DR Hằng Và Dr Nam Tổng Hợp Bài Giảng

ĐẠI HỌC QUỐC GIA TP.
HCM CỘNG HÒA XÃ HỘI CHỦ NGHĨA VIỆT NAM
KHOA Y Độc lập – Tự do – Hạnh phúc
ĐỀ CƯƠNG CHI TIẾT MÔN HỌC

1. Tên môn học: Tế bào và Sinh học Phân tử
Mã môn học:
Thuộc khối kiến thức: Đại cương
2. Số tín chỉ: 3 Lý thuyết: 2 Thực hành: 1
3. Trình độ: Sinh viên năm 1
4. Phân bổ thời gian: Học kỳ II, năm 1
5. Điều kiện tiên quyết: Không
6. Bộ môn tham gia giảng dạy: Sinh hóa – Sinh học Phân tử
7. Mục tiêu học tâp/ Chuẩn đầu ra:
Sau khi học xong môn học này sinh viên có khả năng sau:
Mục tiêu đào tạo Chuẩn đầu ra
Kiến thức
1. Mô tả được cấu trúc, chức năng các thành phần của tế bào. KT1
2. Trình bày được các phương thức vận chuyển qua màng tế bào,
nguyên lý chung của truyền tín hiệu tế bào và các con đường truyền
tín hiệu tế bào
3. Trình bày được chu kỳ tế bào, các cơ chế kiểm soát chu kỳ tế bào và
các kiểu phân bào, các đặc điểm cơ bản của tế bào gốc, tế bào ung thư.
4. Mô tả được cấu trúc và sự sao chép DNA, các quá trình phiên mã,
dịch mã và điều hòa biểu hiện gen.
5. Trình bày được các nhóm bệnh lý di truyền nhiễm sắc thể và di
truyền đơn gen, các phương pháp, kỹ thuật, công nghệ hiện đại trong
nghiên cứu, chẩn đoán và điều trị các bệnh di truyền.
Kỹ năng
1. Sử dụng được kính hiển vi, thực hiện làm tiêu bản và quan sát các
quá trình co, hồi nguyên sinh, quá trình phân bào dưới kính hiển vi.
2. Sử dụng được các dụng cụ, thiết bị cơ bản của sinh học phân tử,
thực hiện được các thí nghiệm tách chiết DNA, PCR, điện di DNA
theo quy trình có sẵn.
3. Tự chuẩn bị bài trước khi đến lớp và giải quyết các chủ đề liên quan
đến môn học (bài tập nhóm).
Thái độ
8. Mô tả vắn tắt nội dung môn học
Môn học cung cấp kiến thức cơ bản về tế bào như cấu trúc, chức năng các thành phần của
tế bào, các quá trình cơ bản xảy ra trong tế bào như vận chuyển qua màng, dẫn truyền tín
hiệu, sinh sản và chết đi; về cơ sở di truyền ở cấp độ phân tử như cấu trúc, sao chép và
sửa sai DNA; quá trình phiên mã, tổng hợp protein, từ đó làm tiền đề cơ bản để áp dụng
trong Y Dược học hiện đại.
9. Tài liệu tham khảo
[1] Albert el al., Essential Cell Biology (5th Edition), Garland Science, 2019
[2] Kaplan, Biochemistry and Medical Genetics (Step 1 lecture Notes), 2021
[3] Hartwell et al., Genetics: From Genes to Genomes (4th Edition), McGraw-Hill
Education, 2010
10. Nhiệm vụ của sinh viên
- Sinh viên dự lớp đúng giờ và đầy đủ.

- Sinh viên không đủ điều kiện dự thi khi:
 Vắng mặt (có và không có lý do) quá 30% tổng số tiết lý thuyết quy định.
 Vắng mặt có lý do quá 30% số giờ thực hành và vắng mặt không lý do quá 20% số
giờ thực hành (bài tập, thảo luận, thí nghiệm, thực tập,…).
 Vắng 50% số lần kiểm tra của môn học.
11. Phương thức đánh giá và cho điểm

Điểm thành
Hình thức Ghi chú
phần
(2) (3)
(1)
Trong đó:
- Điểm báo cáo seminar nhóm

(10%)
- Điểm trung bình các bài thực
Điểm quá
hành (nhóm: 10%) : kết quả
trình/thực hành
Điểm tổng thực hành + báo cáo, giải
(30%)
kết môn thích kết quả thực hành
học - -Điểm 1 bài kiểm tra cá nhân
(0) cuối kỳ (10%): lý thuyết thực
hành
Trong đó:
Điểm giữa kỳ - Điểm chuyên cần (10%),
(20%) - thảo luận, phát biểu xây dựng
bài, bài tập tại lớp… (10%)
Điểm cuối kỳ - Điểm thi cuối kỳ (Trắc

(50%) nghiệm)
Lưu ý:
- Các điểm thành phần được làm tròn đến 0,1

- Điểm tổng kết môn học được làm tròn đến 0,5 (điểm lẻ dưới 0,25 được làm tròn
thành 0,0; điểm lẻ từ 0,25 đến dưới 0,75 được làm tròn thành 0,5; điểm lẻ từ 0,75
đến dưới 1,0 được làm tròn thành 1,0).
11.2. Thang điểm đánh giá thành quả học tập:
Thang điểm và cách xếp loại thành quả học tập như sau:
Thang điểm hệ 4
Xếp loại Thang điểm hệ 10 Thang điểm hệ 100
Điểm số Điểm chữ
Xuất sắc Từ 9,0 đến 10,0 Từ 90 đến 100 4,0 A+
Giỏi Từ 8,0 đến cận 9,0 Từ 80 đến cận 90 3,5 A
Khá Từ 7,0 đến cận 8,0 Từ 70 đến cận 80 3,0 B+
Trung bình khá Từ 6,0 đến cận 7,0 Từ 60 đến cận 70 2,5 B
Trung bình Từ 5,0 đến cận 6,0 Từ 50 đến cận 60 2,0 C
Yếu Từ 4,0 đến cận 5,0 Từ 40 đến cận 50 1,5 D+
Từ 3,0 đến cận 4,0 Từ 30 đến cận 40 1,0 D

Kém
< 3,0 Dưới 30 0,0 F
11.3. Các lưu ý:
- Sinh viên rớt phần nào thì đăng ký học lại phần đó vào khóa sau.
- Điểm môn học được đánh giá là đạt khi có điểm tổng kết môn học từ 5,0 trở lên hoặc
có điểm MT (miễn thi) hay điểm DT (điểm đạt).
12. Chính trực trong học thuật
Sinh viên không được gian lận dưới bất cứ hình thức nào, nhất là đạo văn. Sinh viên sẽ bị
xem là đạo văn nếu:
- Sao chép nguyên văn một câu hay một đoạn văn mà không đưa vào ngoặc kép và
không có trích dẫn phù hợp.
- Sử dụng toàn bộ hay một phần bài viết của người khác.
- Tự đạo văn (self-plagiarize) bằng cách sử dụng toàn bộ hoặc phần nội dung chủ yếu
của một đề tài, báo cáo, bài kiểm tra do chính mình viết để nộp cho hai (hay nhiều)
lớp khác nhau.
Bất kỳ hành động không chính trực nào của sinh viên, dù bị phát hiện ở bất kỳ thời điểm
nào (kể cả sau khi điểm đã được công bố hoặc kết thúc môn học) đều sẽ bị điểm 0 đối
với phần kiểm tra tương ứng, hoặc điểm 0 cho toàn bộ môn học tùy vào mức độ. Ngoài
ra, tùy vào tính chất và mức độ nghiêm trọng của hành động không chính trực, Khoa Y
cũng sẽ xử lý học vụ theo quy chế hiện hành.
13. Nội dung học tập:
13.1. Lý thuyết:
Hình thức dạy

học Giảng viên phụ trách
TT Nội dung
Tự Tài liệu sử dụng
LT TH
học
I/ Section I: Cell Biology
Tế bào: cấu trúc và chức - Giảng viên: TS. Đỗ Thị Thu Hằng
năng (Cells: structure and - TLTK: Albert el al., Essential Cell
1 4 8
function) Biology (5th Edition), Garland Science,
2019
Các thành phần hóa học - TLTK: Albert el al., Essential Cell
2 của tế bào (Chemical 8 Biology (5th Edition), Garland Science,
components of cells) 2019

- Giảng viên: TS. Đỗ Thị Thu Hằng
Sự vận chuyển qua màng tế
bào (Membrane transport) - TLTK: Albert el al., Essential Cell
3 3 8
Biology (5th Edition), Garland Science,
2019
Các khoang ngăn nội bào - TLTK: Albert el al., Essential Cell
và vận chuyển protein Biology (5th Edition), Garland Science,
4 (Intracellular 8 2019
compartments and Protein
transport)
- Giảng viên: TS. Nguyễn Minh Nam

Sự truyền tín hiệu tế bào
(Cell Signaling) - TLTK: Albert el al., Essential Cell
5 4 8
Biology (5th Edition), Garland Science,
2019
Chu kỳ tế bào và các kiểu - Giảng viên: TS. Nguyễn Minh Nam
phân bào, sự chết của tế - TLTK: Albert el al., Essential Cell
bào theo chương trình; Cơ Biology (5th Edition), Garland Science,
sở nhiễm sắc thể của di 2019
6 truyền (Cell cycle, cell 3 8
division, propram cell
death; chromosomal basis
of inheritance)
Quần thể tế bào: mô, tế - TLTK: Albert el al., Essential Cell

7 bào gốc và ung thư (Cell 8 Biology (5th Edition), Garland Science,
communities: tissues, stem 2019
cells and cancers)
II/ Section II: Molecular Biology and Medical Genetics

Cấu trúc DNA, sao chép và - TLTK: Kaplan, Biochemistry and
sửa sai (DNA: structure, Medical Genetics (Step 1 lecture
8 4 8
replication and repair) Notes), 2021; Albert el al., Essential
Cell Biology (5th Edition), Garland
Science, 2019

Phiên mã và dịch mã - TLTK: Kaplan, Biochemistry and
(transcription and Medical Genetics (Step 1 lecture
9 4 8
translation) Notes), 2021; Albert el al., Essential
Cell Biology (5th Edition), Garland
Science, 2019
- Giảng viên: TS. Bùi Chí Bảo

Điều hòa biểu hiện gen
(Regulation of gene - TLTK: Albert el al., Essential Cell
10 2 8 Biology (5th Edition), Garland Science,
expression)
2019; Hartwell et al., Genetics: From
Genes to Genomes (4th Edition), 2010
- Giảng viên: TS. Bùi Chí Bảo

Các chiến lược gen trong - TLTK: Kaplan, Biochemistry and
11 điều trị (Genetic strategies 2 8 Medical Genetics (Step 1 lecture
in therapeutics) Notes), 2021; Hartwell et al., Genetics:
From Genes to Genomes (4th Edition),
2010
Sự tiến hóa của gen và bộ - TLTK: Albert el al., Essential Cell

12 gen (How genes and 8 Biology (5th Edition), Garland Science,
genome evolve) 2019
- Giảng viên: ThS.BS. Trần Thị Kim

Vân
Di truyền học tế bào
13 2 8 - TLTK: Kaplan, Biochemistry and
(cytogenetics)
Medical Genetics (Step 1 lecture
Notes), 2021
- Giảng viên: ThS.BS. Trần Thị Kim

Vân
Di truyền học đơn gen
14 2 8 - TLTK: Kaplan, Biochemistry and
(single-gene disorders)
Medical Genetics (Step 1 lecture
Notes), 2021
Tổng cộng 30 96
Lưu ý: Bài 10 và 11 gộp chung thành 1 buổi, bài 13 và 14 gộp chung thành 1 buổi
13.2. Thực hành
Hình thức dạy

học Giảng viên phụ trách
TT Nội dung
Tự Tài liệu sử dụng
LT TH
học
-Giảng viên: ThS. Huỳnh Thị Diệu
Hiền; ThS. Đă ̣ng Thi ̣Hà Thanh
Kính hiển vi quang học (Light
microscope) -Giáo trình thực tập Sinh học Đại
1 5 5
Cương 2017, Biên soạn bởi Đỗ Thị
Thu Hằng, Huỳnh Thị Diệu Hiền
(lưu hành nội bộ)
-Giảng viên: ThS. Huỳnh Thị Diệu

Quan sát các quá trình nguyên Hiền; ThS. Đă ̣ng Thi ̣Hà Thanh
phân và thẩm thấu -Giáo trình thực tập Sinh học Đại
2 5 5
(Observation of osmosis and Cương 2017, Biên soạn bởi Đỗ Thị
mitosis) Thu Hằng, Huỳnh Thị Diệu Hiền
Giới thiệu các dụng cụ thiết bị -Giảng viên: ThS. Huỳnh Thị Diệu
cơ bản trong phòng thí Hiền; KS. Nguyễn Thi ̣Quỳnh Mai
nghiệm SHPT (Introductions -Giáo trình thực tập Sinh học Đại
to basic tools and equipments Cương 2017, Biên soạn bởi Đỗ Thị
in molecular biology lab) Thu Hằng, Huỳnh Thị Diệu Hiền
Các phương pháp đánh giá (lưu hành nội bộ)
3 5 5
nucleic acid và điện di nucleic
acid trên gel agarose
(Determine the concentration

& purity of nucleic acids;
Agarose electrophosis of
nucleic acid )
-Giảng viên: TS Đỗ Thị Thu Hằng;
ThS. Huỳnh Thị Diệu Hiền
Tách chiết nucleic acid -Giáo trình thực tập Sinh học Đại
4 5 4
(Nucleic acid extraction) Cương 2017, Biên soạn bởi Đỗ Thị
-Giảng viên: TS Đỗ Thị Thu Hằng;

ThS. Huỳnh Thị Diệu Hiền
-Giáo trình thực tập Sinh học Đại

5 Kỹ thuật PCR (PCR method) 5 5
Cương 2017, Biên soạn bởi Đỗ Thị
Rối loạn các cơ chế phân -Giảng viên: TS Đỗ Thị Thu Hằng;
tử, tế bào trong các bệnh lý TS Nguyễn Minh Nam
ở người và cập nhật các
tiến bộ gần đây trong y
sinh học phân tử
7 5 5
(Dysfunction of cellular
and molecular mechanisms
and human diseases and
Recent advances in
molecular biomedicine)
Tổng cộng 30 30
TP. HCM, ngày tháng năm 2022

TRƯỞNG KHOA
GS.TS.BS. ĐẶNG VẠN PHƯỚC

Introduction to the subject
• Why do you need to study this subject?

• What will you study in this subject?
• How will you be evaluated/assessed?
CELL & MOLECULAR BIOLOGY
Cell Biology: Unit 1
THE OVERVIEW OF CELLS:

STRUCTURES AND FUNCTIONS
Lecturer: Đỗ Thị Thu Hằng

Email: dtthang@medvnu.edu.vn
REFERENCE
• Essential Cell Biology (5th Edition, 2019)

written by Albert et al., …, Chapter 1
• Other sources
MAIN CONTENTS
1. OVERVIEW OF CELL AND CELL THEORY

2. TWO TYPES OF CELL AND BIODIVERSITY OF THE EARTH
3. CELL STRUCRURES AND FUNCTIONS
4. ORIGIN AND EVOLUTION OF LIFE ON EARTH
5. SOME DISCUSSIONS
6. MICROSCOPE
• Smallest living unit
•
1/ OVERVIEW OF CELL •
Most are microscopic
Vary enormously in appearance and function
AND CELL THEORY • All have a similar basic chemistry
– Size of SARS-CoV-2?
– What is the filter size of N95 mask? Why wearing masks such
as N95 mask efficiently prevent SARS-CoV-2 infection?
Discovery
of Cells
Robert Hooke - 1665
– Observed sliver of cork
with simple compound
microscope
(magnifications of 30x
to 50x)
– Saw “rows of empty
boxes”
– Coined the term “cell”
Anton van Leeuwenhoek - 1674
- Made use of a
microscope containing
improved lenses that
could magnify objects
almost 300-fold
- Observed living
organisms (bacteria,
sperms, blood cells…)
Oral bacteria observed by Anton van Leeuwenhoek
and their contemporary equivalents
(Microbiol. Mol. Biol. Rev. December 2007 vol. 71 no.
4653-670)
Matthias Schleiden, 1839:
Suggested that every structural part of a plant was made up of cells or
the result of cells.
Theodor Schwann, 1839:

Stated that along with plants, animals are composed of cells or the
product of cells
Rudolf Virchow, 1855:

Stated that all cells arise only from pre-existing cells.
Three tenets of cell theory:
1. All living things are made of cells
2. The cell is the most basic unit of life
3. All cells arise only from pre-existing cells
The modern version of the cell theory:

The modern version of the cell theory includes the ideas
that:
1. All cells have the same basic chemical composition
2. Energy flow occurs within cells.
3. Heredity information (DNA) is passed on from cell to cell
2. TWO TYPES OF CELLS AND BIODIVERSITY OF THE
EARTH
Biological classification
Kingdom: Animalia
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Tribe: Hominini
Genus: Homo
Species: H. sapiens
there may be up to 100 million distinct species of living things on our

planet
Despite of the diversity in organisms, there are only two broad types
of cell: Prokaryotic cells and Eukaryotic cells
Similarity Difference
• Plasma membrane: a surrounding membrane • Membrane-bound
• Cytoplasm – cell contents in thick fluid, containing ribosomes organelles (including
• Control center with DNA nucleus)
Domain Bacteria includes
prokaryotes in the kingdom
Bacteria.
• One of largest groups on

Earth
• Classified by shape, need
for oxygen, and diseases
caused
Domain Archaea includes prokaryotes in the kingdom
Archaea pseudomurein, complex carbohydrates, or protein-
glycoproteins
• Cell walls chemically
different from bacteria
• Differences discovered
by studying rRNA
• Known for living in
extreme environments
Why don’t archaea cause disease? | M

icrobiology
Society Hot Springs, Midway & Lower Geyser Basin, Yellowstone
(https://microbiologysociety.org/blog/ National Park. This photo shows steam rising from hot
why-dont-archaea-cause-
disease.html)
and sterile deep blue water center surrounded by huge
mats of archaea
Domain Eukarya includes all eukaryotes.
• Kingdom Protista
• Kingdom Plantae
• Kingdom Fungi
• Kingdom Animalia
Figure 9
Comparing the 6 kingdoms
3/ CELL STRUCTURES AND
FUNCTIONS
3.1/ CELL STRUCTURES AND FUNCTIONS
IN EUKARYOTE
Cell membranes
• Cell membranes include plasma membrane and
organelle membranes
 Plasma membrane/cell surface membrane:
 defines the boundary of the cell  vital for life
 regulates the movement of materials into and out
of the cell
 facilitates signaling between cells
 Organelle membranes:
 define the boundaries of organelles
 provide a matrix upon which complex chemical
reactions can occur.
Cytoplasm
• Viscous fluid containing organelles
• Suspending cellular structures and providing a
place for cellular functions to take place
• Components of cytoplasm
– Interconnected filaments & fibers
– Fluid = cytosol
– Organelles
– Storage substances
Organelle
Organelles
• Organelle: A specialized subunit within a cell that has a specific
function, and is usually separately enclosed within its own
membrane.
• Two general kinds:
– Double membrane organelles: Mitochondria and chloroplast (bacteria-
like organelles), and nucleus
– Single membrane organelle (derived from membranes): ER, Golgi…
ORGANELLES BOUNDED BY
DOUBLE-MEMBRANE ENVELOPES
Nucleus
• Is often the most prominent
cell organelle
• Control center of cell
• Double membrane, have

pores on membrane
• Contains
– Chromosomes: store
genetic material (DNA)
– Nucleolus: makes
ribosome
Bacteria-Like Organelles
• Release & store energy
- Mitochondria: release energy
- Chloroplasts: store energy
• Have small circular DNA molecules that are similar
to the chromosomes of bacteria
• Both contain ribosomes and synthesize a small
subset of their own proteins
Mitochondria
* Function: Is cell’s power stations: release energy (ATP) by breaking
down fuel molecules (cellular respiration) such as glucose, fatty acids
* Structure:
 Outer membrane:
 Protects the mitochondria
 Lets small molecules in and out
 Inner membrane:
 Contains proteins that function to make ATP
 Cristae:
 Infolded parts of inner membrane
 Increase the area available to have reactions with make ATP
 Matrix:
 Contains proteins and mitochondrial DNA
 Helps with making ATP
Mitochondrial structure
An electron micrograph of a cross section of a mitochondrion

reveals the extensive infolding of the inner membrane.
Chloroplasts
 Function: Is solar energy capturing organelle: makes cellular
food – glucose via photosynthesis
 Structure:
 Stacked sacs (thylakoids) contain the green pigment
chlorophyll and other molecules responsible for light
capture
 The dark reactions of photosynthesis takes place in the
matrix, called the stroma, which also contains the DNA and
ribosomes.
ORGANELLES BOUNDED BY
SINGLE-MEMBRANE ENVELOPES
• Eukaryotic cells contain many sacs and tubes

bounded by a single membrane.
• Although these are often rather similar in
appearance, they can be subdivided into different
types specialized to carry out distinct functions.
Peroxisomes
• Involved in the formation and decomposition of hydrogen
peroxide (H2O2) involved in oxidization of substrates like
phenols, formic acid, formaldehyde, and alcohol
• breakdown of very long chain fatty acids through beta oxidation
RH2 + O2 ==>> R + H2O2

R: Specific organic substrates
H2O2 + R'H2 ==>> R' + 2H2O

R’: toxic substrates
oxidative enzymes
2H2O2 ==>> 2H2O + O2 such as catalase, D-
amino acid oxidase
and uric acid oxidase
https://scienceaid.net/the_Structure_and_Function_of_Peroxisomes
Endoplasmic reticulum (ER)
• The ER
functions as a
manufacturing
and packaging
system.
• ER is
connected to
the nucleus
and it works
closely with
the Golgi
apparatus.
Rough Endoplasmic Reticulum
• Make the proteins (in ribosome) that will end
up as integral membrane proteins in the
plasma membrane, and proteins that the cell
will export to the extracellular medium (such
as the proteins of the extracellular matrix), as
well as lysosomal enzymes.
• Alter proteins and fold protein into correct
shape
Smooth Endoplasmic Reticulum
• Synthetize lipids and steroids (Ex: hormones in the ovaries,
testes, and the adrenal gland)
• Breaks down toxic substances including drugs (Ex: in the liver)
using detoxifying enzymes (e.g., cytochrome P450 enzymes)
• Storage and sudden release of calcium ions
(*ions are pumped from the cytosol into the lumen of the
smooth endoplasmic reticulum to more than 100 times
the concentration found in the cytosol. Many stimuli can
cause this calcium to be released back into the cytosol,
where it activates many cell processes)
Golgi Apparatus
• Packaging & shipping
station of cell
• Is a distinctive stack of
flattened sacks called
cisternae.
• Is the distribution point
of the cell where proteins
made within the rough
endoplasmic reticulum
are further processed
and then directed to their
final destination
Lysosomes
– Sometimes called “cell
stomachs” because
they contain enzymes
that digest cellular
components.
– Plentiful in cells that
digest and destroy
other cells, such as
macrophages
– Aid in cell renewal,
break down old cell
parts and digests
invaders
The endomembrane system
Endosomes
Endosomes are the integral parts of the endocytic process, and thereby, play crucial roles in
various physiological processes, such as nutrient uptake, sorting and delivery of
macromolecules, and regulation of cell surface receptors and transporter expressions.
Vacuoles
• Membrane bound storage sacs
• More common in plants than animals
• Contents
– Water
– Food
– wastes
Cilia & Flagella
• Provide motility
• Core of microtubules
wrapped in plasma
membrane
• Cilia (tiny hairs)
– Shorter and more numerous
than flagella
– Used to move fluids across
surfaces by producing sweeping
movements
• Flagella (tails)
– Longer
– Usually one per cell
– Propel cells via undulating whip
like movement
Cilia & Flagella Structure
• Bundles of microtubules
• Wrapped in plasma membrane
Remember 9 (pairs)
+ 2 (single)
Other cell structures
Cell Walls
• Found in plants, fungi, & many protists
• Surrounds plasma membrane
• Plant cell walls are composed of cellulose
plus other polysaccharide molecules such
as hemicellulose and pectin.
• Gives shape to the cell and structural
rigidity to the organism
Centrosome
• Structure: nine triplets of microtubes form one centriole;
Two centrioles form one centrosome
• Function: forms spinde fibres to seperate chromosomes
during cell division
Cytoskeleton
• Eukaryote cytoskeleton is
made of 3 fiber types
– Microfilaments (thread-like)
– Microtubules (tube-like)
– Intermediate filaments
• Functions:
– Supports and shapes the cell
The
– Anchor organelles (held in their eukaryotic
relative locations) and move cytoskeleton.
substances/vesicles/organelles. These Actin
movements are driven by motor filaments are
proteins that use the energy of ATP shown in red,
hydrolysis to propel the organelles and and
vesicles along the filaments microtubules
– Support cell movement (forming composed of
flagella and cilia) beta tubulin
– Support cell division (forming are in green.
centrioles)
The Extracellular Matrix (ECM)
• Is the extracellular part of animal tissue:
 Provides mechanical support
 Separates different tissues
 Generate signals that maintain cell
survival
 Substrate for cell migration
• Contains 3 classes of molecule:
 Structural proteins (collagens and
elastins)
 Protein-polysacharide complexes
(proteoglycan) to embed the
structural proteins
 Adhesive proteins to attach cells to
matrix (fibronectin, laminin)
Cell Junctions
• In multicellular organisms, and particularly in epithelia,
neighboring cells within a tissue are usually connected
together via cell junctions.
• In animal cells there are three types of junctions:
 Tight junctions (occluding junctions)
 Gap junctions (communicating junction):
 Anchoring junctions:
Adherens junctions:
Desmosomes:
Hemidesmosome:
Types of cell Junctions in epithelia and their functions
Tight junctions are found wherever flow of extracellular medium is to be restricted
and are particularly common in epithelial cells such as those lining the small intestine.
The plasma membranes of adjacent cells are pressed together so tightly that no
intercellular space exists between them. Tight junctions between the epithelial cells of
the intestine ensure that the only way that molecules can get from the lumen of the
intestine to the blood supply that lies beneath is by passing through the cells, a route
that can be selective. Another example is tight junctions between the epithelial cells
lining your bladder prevent urine from leaking out into the extracellular space
• Gap junctions allow solute
and electrical current to
pass from the cytosol of
one cell to the cytosol of its
neighbor.
• When two cells form a gap
junction, ions and small
molecules can pass
directly from the cytosol of
one cell to the cytosol of
the other cell without going
into the extracellular fluid
• Gap junctions are
especially important in the
heart, where they allow an
electrical signal to pass
rapidly between all the
cardiac muscle cells,
ensuring that they all
contract at the proper time
Diseases of organelles
• Lysosomes: Tay – Sachs disease, Gaucher disease, Pompe disease
• Mitochondria: Leigh syndrome, MELAS, Alpers Disease …
• Peroxisome: X-linked adrenoleukodystrophy, Zellweger syndrome
(ZS),
Refsum disease…
• Golgi body: Amyotrophic lateral sclerosis, Alzheimer's disease,
Parkinson's disease …
• ER: Cystic fibrosis…
• Plasma membrane: Cystic fibrosis, Diabetes, and Familial
Hypercholesterolemia…
Mitochondrial diseases
• occur when mitochondria fail to produce enough energy for the
body to function properly
• often chronic and genetic (except for secondary mitochondrial
dysfunction)
• can affect almost any part of the body but the parts of your body
that need the most energy – heart, brain, muscles – are most
affected by mitochondrial disease.
• at least 350 different types of mitochondrial disease have been
reported with the potential for 100s more.
• One in 5,000 individuals has a genetic mitochondrial disease.
• Inheritance modes: autosomal recessive, autosomal dominant
mitochondrial inheritance, X-linked recessive inheritance, random
(de-novo) mutations
37 MTDNA GENES
• MT-ATP6, MT-ATP8, MT-CO1, MT-CO2, MT-CO3, MT-CYB, MT-ND1, MT-ND2, MT-ND3, MT-ND4, MT-
ND4L, MT-ND5, MT-ND6, MT-RNR1, MT-RNR2, MT-TA, MT-TC, MT-TD, MT-TE, MT-TF, MT-TG, MT-TH,
MT-TI, MT-TK, MT-TL1, MT-TL2, MT-TM, MT-TN, MT-TP, MT-TQ, MT-TR, MT-TS1, MT-TS2, MT-TT, MT-
TV, MT-TW, MT-TY.
• Lysosomal storage disorders are a group of over 50 rare inherited metabolic
disorders that result from defects in lysosomal function
• If one lysosomal enzymes is defective due to a mutation, the large molecules
accumulate within the cell, eventually killing it
• the incidence is about 1:5,000
• affect mostly children and they often die at a young age, many within a few months
or years of birth.
• Most lysosomal storage disorders are inherited in an autosomal recessive manner.
3.2/ CELL STRUCTURES AND FUNCTIONS
IN PROKARYOTE
Vỏ ngoài
Differentiation between G+ and G- by Gram staining method
4. ORIGIN AND EVOLUTION OF LIFE ON EARTH
It seems highly likely that eukaryotes
evolved from prokaryotes
• The endosymbiotic theory states that several
key organelles of eukaryotes originated
as symbioses between separate single-celled organisms.
For example, mitochondria would have originated as
free-living aerobic bacteria and chloroplasts as
cyanobacteria, which are photosynthetic prokaryotes
formerly known as blue-green algae.
• Differently, the nuclear membranes and the membranes
of the ER, Golgi apparatus, endosomes, and lysosomes
most likely originated by invagination of the plasma
membrane
Mitochondria are thought to have evolved from engulfed bacteria. It is virtually certain that
mitochondria evolved from aerobic bacteria that were engulfed by an archaea-derived, early anaerobic
eukaryotic cell and survived inside it, living in symbiosis with their host. As shown in this model, the
double membrane of present-day mitochondria is thought to have been derived from the plasma
membrane and outer membrane of the engulfed bacterium; the membrane derived from the plasma
membrane of the engulfing ancestral cell was ultimately lost
Nuclear membranes and the ER may have evolved through invagination of the plasma membrane. In
bacteria, the single DNA molecule is typically attached to the plasma membrane. It is possible that in
a very ancient prokaryotic cell, the plasma membrane, with its attached DNA, could have invaginated
and, in subsequent generations, formed a two-layered envelope of membrane completely
surrounding the DNA. This envelope is presumed to have eventually pinched off completely from the
plasma membrane, ultimately producing a nuclear compartment penetrated by channels called
nuclear pores, which enable communication with the cytosol. Other portions of the invaginated
membrane may have formed the ER, which would explain why the space between the inner and
outer nuclear membranes is continuous with the ER lumen.
5. SOME DISCUSSION
Are VIRUSES living organisms?
• Viruses occupy a unique position between the living
and nonliving worlds:
• They are made of the same molecules as living cells
• But they are incapable of independent existence,
completely dependent on a host cell for reproduction.
• Almost all living organisms have viruses that infect
them
• Bacterial viruses called bacteriophages, are used by
scientists to transfer genes between bacterial strains
Structure of viruses contain the following components:
• Nucleic acids: DNA or RNA
• Capsid: made from protein
• Envelope: made from lipids when virus exits cell (No enveloped 
naked)
• The entire infectious virus particle, called a virion, consists of the
nucleic acid and capsid, and sometimes, the envelope.
• The structure and composition of these components can vary widely.
The structure of SARS-CoV-2 (

Coronavirus Disease 2019–COVID
-19 | Clinical Microbiology Reviews (asm.org)
The coronavirus
virion
and life cycle.
cell surface serine
protease TMPRSS2
ER-to-Golgi
intermediate
compartment
(ERGIC)
double-
membrane
vesicles (DMVs),
convoluted
membranes
(CMs) and small
open double-
membrane
spherules (DMSs
Source:
https://doi.or
g/10.1038/s4
1579-020-
00468-6
Targeting the viral life cycleThe SARS-CoV-2
life cycle begins with entry into the host cell,
followed by generation of the RTC derived from
pp1a translated from ORF1a, and pp1ab
translated by ribosomal frameshifting to ORF1b.
Then, the viral genome is replicated and
packaged into new virions. Inhibitors (red)
targeting viral and host factors that are
important in the viral life cycle could prevent the
spread of infection.
Science 26 Feb 2021:

Vol. 371, Issue 6532, pp. 884-885
Can we culture the cells in lab?
Cells in culture often display properties that reflect their origin. These phase-contrast
micrographs show a variety of cell types in culture. (A) Fibroblasts from human skin. (B)
Human neurons make connections with one another in culture. (C) Epithelial cells from
human cervix form a cell sheet in culture. (Micrographs courtesy of ScienCell Research
Laboratories, Inc.)
Fig. 1. Infection of macrophages with influenza
virus. One day before infection, mouse alveolar
macrophages and Raw264.7 macrophages were
seeded onto 8 well-chambered cover glass so
that the cell density was about 70% confluent at
the time of infection. The next day, cells were
infected with PR8 (MOI = 2). After absorption
for 1 h at 37 ◦C, the cells were washed and
cultured for further 8 h. The cells were then
washed again, fixed, and immunostained with
anti-SIV mouse Ab as described in Section 4.
Immunofluorescence was detected with an
Olympus FV10C-CU. Bar, 10 mm. The data
shown are representative of three independent
experiments, all with similar results
Note:PR8 = A/Puerto-Rico/8/34 (H1N1)

CÂU HỎI ÔN TẬP
1. Khái quát các đặc điểm chính của tế bào
2. Tóm tắt quá trình khám phá ra tế bào, sự thành học thuyết tế bào; phát biểu
học thuyết tế bào
3. So sánh cấu trúc của tế bào nhân sơ và nhân thực. Giải thích tại sao các virus (ví
dụ SARS-CoV-2) không được xem là các sinh vật sống và không có cấu trúc tế bào
4. Nêu hệ thống phân loại 3 vực và 6 giới sinh vật và khác biệt cơ bản giữa các giới
sinh vật; Các bào quan tế bào nhân thực đã được hình thành như thế nào trong
quá trình tiến hóa
5. Mô tả cấu trúc và chức năng của màng tế bào
6. Mô tả ngắn gọn cấu trúc và chức năng của các bào quan màng đơn và màng kép.
7. Hệ thống nội màng là gì, có chức năng gì? bao gồm các thành phần nào?
8. So sánh giữa hệ khung xương tế bào và chất nền ngoại bào
9. Liệt kê các thành phần cấu trúc của tế bào nhân sơ và chức năng của chúng. Nêu
khác biệt cơ bản trong cấu trúc vi khuẩn Gram (-) và Gram (+) và giải thích độc
tính của màng ngoài vi khuẩn Gram
10.So sánh 3 loại kính hiển vi: kính hiển vi ánh sáng, kinh hiển vi điện tử, kính hiển
vi hùynh quang về độ phóng đại và mục đích sử dụng
Self-studying
6. Microscope The History
• The Greeks & Romans used “lenses” to magnify objects over 1000
years ago.
• Hans and Zacharias Janssen of Holland in the 1590’s created the
“first” compound microscope (=consisting of two convex lenses )
with magnification ~9X
Zacharias Jansen
The “First” Microscope 1588-1631
The History
• Anthony van Leeuwenhoek and Robert Hooke made
improvements by working on the lenses
Anthony van Leeuwenhoek Hooke Microscope Robert Hooke

1632-1723 1635-1703
How a Microscope Works
Convex Lenses
bend light and
focus it in one
spot.
Magnification
• Magnification
– enlargement of an object
– compare size of image to actual size of object
• Total magnification
– ocular power x objective power = total magnification
• Generally, three or four objective lenses are found on a
microscope, with ranges of 10X, 40X, 100X powers. The
shortest lens is of the lowest power, and the longest lens is
high power lenses.
• Eyepiece lens usually contains a magnification of 10X or
25X
Resolution
• Resolution – capacity to
show 2 points that are
close together as
separate
• The increase in
magnifying power of
the objective depends
on its resolving power.
Poor Resolution = Blurry Image

Good Resolution = Clear Image
Major types of microscope
• The Light Microscope

– Bright-field microscopy
– Phase-contrast microscopy
• The Electron Microscope
– Transmission electron microscope
– Scanning Electron Microscope
• Fluorescent microscope
6.1/ Light
Microscope
– 1st type of
microscope,
most widely
used
– Light passes
through 2
lenses
• Most living cells have
little color and are
therefore largely
transparent to
transmitted light. The
use of phase-contrast
microscopy. relies on
the fact that light
travels at different
speeds through regions
of the cell that differ in
composition. The
phase-contrast
microscope converts
these differences in
refractive index into
differences in contrast,
and considerably more
detail is revealed
6.2/ Electron Microscope
• Used to observe VERY small objects: viruses,
DNA, parts of cells
• Uses beams of electrons rather than light
• Much more powerful
• Includes SEM (used to look at the surface detail
of cells and other structures)
and TEM (used to look structure inside the cells
and other structures)
• Can magnify up to 100,000 - 250,000x
The transmission electron microscope (TEM) is in principle similar to
a light microscope, but it uses a beam of electrons instead of a
beam of light, and magnetic coils to focus the beam instead of glass
lenses. The specimen, which is placed in a vacuum, must be very
thin. Contrast is usually introduced by staining the specimen with
electron-dense heavy metals that locally absorb or scatter electrons,
removing them from the beam as it passes through the specimen.
The TEM has a useful magnification of up to a million-fold and can
resolve details as small as about 1 nm in biological specimens.
a small region of a cell in a

piece of testis by TEM. The
tissue has been chemically
fixed,
embedded in plastic, and
cut into very thin sections
that have then been
stained with salts of
uranium and lead.
In the scanning electron
microscope (SEM), the specimen,
which has been coated with a very
thin film of a heavy metal, is
scanned by a beam of electrons
brought to a focus on the specimen
by magnetic coils that act as lenses.
6.3/ Fluorescent Microscope
Self-studying
Chapter 2
COMPONENTS OF CELLS
1. CHEMICAL BONDS
2. SMALL MOLECULES IN CELLS
3. MACROMOLECULES IN CELLS
Câu hỏi: Tế bào có tới 70% là nước, 30% còn lại bao gồm các thành phần gì?
Trình bày ngắn gọn cấu tạo và chức năng của 4 nhóm đại phân tử trong tế bào
Self-studying
Chapter 20
CELLULAR COMMUNITIES: TISSUES, STEM CELLS, AND

CANCER
1. EXTRACELLULAR MATRIX AND CONNECTIVE TISSUES

2. EPITHELIA SHEETS AND CELL JUNCTION
3. STEM CELLS AND TISSUE RENEWAL
4. CANCER
Câu hỏi: Nêu 2 tính chất chính của tế bào ung thư. Tại sao đối với đa số
các loại ung thư, tỉ lệ mắc bệnh tăng theo độ tuổi
Cell Biology: Unit 2
TRANSPORT ACROSS CELL

MEMBRANES

Email: dtthang@medvnu.edu.vn
REFERENCE
Essential Cell Biology (5th Edition, 2019)
written by Albert et al., …, Chapter 12
MAIN CONTENTS
1. PRINCIPLES OF MEMBRANE TRANSPORT
2. TRANSPORTERS AND THEIR FUNCTIONS
3. ION CHANNELS AND THEIR FUNCTIONS
1. PRINCIPLES OF MEMBRANE
TRANSPORT
• To survive and grow, cells must be able to exchange
molecules with their environment. They must import
nutrients such as sugars and amino acids and
eliminate metabolic waste products.
• They must also regulate the concentrations of a variety
of inorganic ions in their cytosol and organelles.
• A few molecules, such as CO2 and O2, can simply
diffuse across the lipid bilayer of the plasma
membrane. But the vast majority cannot and their
transfer depends on specialized membrane transport
proteins
Figure 1. Cell membranes contain specialized membrane transport proteins that facilitate
the passage of selected small water-soluble molecules.
(A) Protein-free, artificial lipid bilayers are impermeable to most water-soluble molecules.
(B) Cell membranes, by contrast, contain transport proteins, each of which transfers a
particular type of molecule. This selective transport can include the active pumping of
specific molecules either out of (purple triangles) or into (green bars) the cell. The
combined action of different transport proteins allows a specific set of solutes to build
up inside a membrane-enclosed compartment, such as the cytosol or an organelle.
“It has long been established that transporters exist for
endogenous compounds such as glucose, amino acids,
nucleosides, water soluble hormones and
neurotransmitters. However, the perspective that
xenobiotics are also substrates of membrane carriers has
emerged only in the last two decades. Xenobiotics are by
definition compounds which are not essential for the
maintenance of a physiological function; they may,
however, modulate, ameliorate or damage such functions,
depending on whether they are drugs, diagnostics, or
toxins”
Source: Ernst Petzinger & Joachim Geyer. Drug transporters in pharmacokinetics.
Naunyn-Schmiedeberg's Archives of Pharmacology volume 372, pages 465–475 (2006)
1.1. Lipid bilayers are impermeable to ions and
most uncharged polar molecules
Figure 2. The rate at which a
molecule crosses a protein-
free artificial lipid bilayer by
simple diffusion depends on
its size and solubility.
- The smaller the molecule and,
more importantly, the less polar it
is, the more rapidly the molecule
diffuses across the bilayer.
- Note that many of the organic
molecules that a cell uses as
nutrients (shaded in red) are too
large and polar to pass directly
through an artificial lipid bilayer
1.2. The ion concentrations inside a cell are very
different from those outside
• Because cell membranes are impermeable to inorganic
ions, living cells are able to maintain internal ion
concentrations that are very different from the
concentrations of ions in the media that surrounds them
• These differences in ion concentration are crucial for a
cell’s survival and function.
• The movement of these ions across cell membranes
plays an essential part in many biological processes, but
is perhaps most striking in the production of ATP by all
cells, and in communication by nerve cells.
• Na+ is the most plentiful positively charged ion (cation) outside the cell, whereas
K+ is the most abundant inside
• The high concentration of Na+ outside the cell is electrically balanced chiefly by
extracellular Cl–, whereas the high concentration of K+ inside is balanced by a
variety of negatively charged organic and inorganic ions (anions) including
nucleic acids, proteins, and many cell metabolites
Table 1
1.3. Differences in the concentration of inorganic
ions across a cell membrane create a membrane
potential
• Although the electrical charges inside and outside the cell are generally kept
in balance, tiny excesses of positive or negative charge, concentrated in the
neighborhood of the plasma membrane, do occur. Such electrical
imbalances generate a voltage difference across the membrane called the
membrane potential
• When a cell is “unstimulated,” the exchange of anions and cations across the
membrane will be precisely balanced. In such steady-state conditions, the
voltage difference across the cell membrane—called the resting membrane
potential—holds steady. But it is not zero. In animal cells, for example, the
resting membrane potential can be anywhere between –20 and –200
millivolts (mV), depending on the organism and cell type.
• Action membrane potential, in contrast, occurs when a cell is “stimulated”.
Changes in membrane potential are the basis of electrical signaling
1.4. Cells contain two classes of membrane
transport proteins: transporters and
channels
• Channels: discriminate mainly on the basis of size and

electric charge: when the channel is open, any ion or
molecule that is small enough and has the appropriate
charge can pass through.
• Transporters: transfer only those molecules or ions
that fit into specific binding sites on the protein.
Figure 3. Inorganic ions and small, polar organic molecules can cross a cell
membrane through either a transporter or a channel.
(A) A transporter undergoes a series of conformational changes to transfer small
solutes across the lipid bilayer  they bind their solutes with great specificity, in
the same way an enzyme binds its substrate
(B) A channel, when open, forms a pore across the bilayer through which
specific inorganic ions or, in some cases, polar organic molecules can diffuse.
 Channels transfer solutes at a much greater rate than transporters.

However, transporter transports are more flexible: transport both inorganic and
organic molecules, and transport both active and passive manner
1.5. Solutes cross membranes by either
passive or active transport
Figure 4. Solutes cross cell membranes by either passive or active transport.

- Some small nonpolar molecules move passively down their concentration gradient
across the lipid bilayer by simple diffusion.
- Most solutes, however, require the assistance of a channel or transporter.
1.6. Both the concentration gradient and
membrane potential influence the passive
transport of charged solutes
Figure 5. An electrochemical gradient
has two components.
-The net driving force (the electrochemical Na+
gradient) tending to move a charged solute
(ion) across a cell membrane is the sum of a
force from the concentration gradient of the
solute and a force from the membrane
potential.
- In (A), the concentration gradient and
membrane potential work together to K+
increase the driving force for movement of
the solute.
- In (B), the membrane potential acts against
the concentration gradient, decreasing the
electrochemical driving force.
1.7. Water moves passively across cell
membranes down its concentration gradient—a
process called osmosis
• Cells are mostly water
• Water can diffuse directly across the lipid
bilayer—although slowly
• Some cells also contain specialized
channel proteins called aquaporins in their
plasma membrane, which greatly facilitate
this flow.
• The total concentration of solute particles
inside the cell—also called its osmolarity—
generally exceeds solute concentration
outside the cell.
• This movement of water down its
concentration gradient is called osmosis.
• Osmosis, if it occurs without constraint,
can make a cell swell. Different cells cope
with this osmotic challenge in different
ways
Figure 6. Cells use different
tactics to avoid osmotic
swelling.
- (A) A fresh water
amoeba avoids swelling
by periodically ejecting
the water
- (B) the plant cell’s tough
cell wall prevents
swelling
* Most animal cells have a gel-like cytoplasm that

resists osmotic swelling.
2. TRANSPORTERS AND THEIR FUNCTIONS
2.1. Each cell membrane has its own characteristic set of

transporters.
Figure 7. Only a few of these are
indicated here. For example:
- The plasma membrane contains
transporters that import nutrients
such as sugars, amino acids
- The lysosome membrane contains
an H+ transporter that imports H+
- The inner membrane of
mitochondria contains transporters
for importing the pyruvate and
transporters for exporting ATP once
it is synthesized.
2.2. Transporters are generally divided into
three main classes:
Transporter can be divided into three main classes:
- Solute carrier (SLC): includes transporters that function by:
 Facilitative diffusion (passive transport). Ex: glucose transporter.
 Secondary active transport (coupled pumps). Ex: (glucose-Na+
symport
- P-type ATPases: pump cations across the membrane using primary
active transport (i.e. ATP energy). Example: Ca2+ pumps (or Ca2+-ATPase)
and the Na+-K+ pump (or Na+-K+ ATPase)
- ATP-binding cassette (ABC): are primary active transporters that use
energy from ATP to transport a wide range of substrates mainly to the
outside of a cell membrane or organelle. Example: CFTR
* Note: transporter carrying active transports commonly named as pump  They

include coupled pumps and ATP-driven pumps (which further include P-type ATPase
and ABC)
2.3. Glucose transporter is an important example
of passive transporters that move a solute along
its electrochemical gradient
• Glucose transporter are found in the plasma membrane of many
mammalian cell types
• Because glucose is uncharged, the direction in which it is transported
is determined by its concentration gradient alone
• When glucose is plentiful outside cells, as it is after a meal, it is
passively transported into the cells.
• When blood glucose levels are low  the glucose is passively
transported out of the liver cells
Figure 8.
Conformational
changes in a
transporter mediate the
passive transport of a
solute such as glucose
2.4. The Na+ pump is an important example of P-
type ATPases in animal cells that uses energy
supplied by ATP to expel Na+ and bring in K+
• The Na+ pump also named as ATP-driven Na+ pump plays such a
central part in the energy economy of animal cells, that it typically
accounts for 30% or more of their total ATP consumption
• This pump uses the energy derived from ATP hydrolysis to
transport Na+ out of the cell as it carries K+ in. The pump is
therefore also known as the Na+-K+ ATPase or the Na+-K+ pump.
• The Na+ pump generates a steep concentration
gradient of Na+ and K+ across the plasma
membrane: the Na+ concentration in the cytosol
about 10–30 times lower than in the extracellular
fluid and the K+ concentration about 10–30 times
higher.
• The Na+ pump functions like a bilge pump in a
leaky ship, continuously expelling the Na+ that is
constantly entering the cell through other
transporters and ion channels in the plasma
membrane.
• The stored energy in Na+ electrochemical gradient
is sufficient to sustain for many minutes the various
pumps
in the plasma membrane that are driven by the
Figure 9. The Na+ pump uses the energy of ATP hydrolysis to pump Na+ out of
animal cells and K+ in. The energy from ATP hydrolysis induces a series of
protein conformational changes that drive the Na+/K+ ion exchange. In this
way, the pump helps keep the cytosolic concentrations of Na+ low and K+ high.
2.5. Glucose-Na+ symport is an example of
secondary active transport (coupled pumps)
Figure 10. A glucose–Na+ symport protein uses the electrochemical Na+

gradient to drive the active import of glucose.
Figure 11. Transporters can function as uniports, symports, or antiports.
- Transporters that carry a single solute across the membrane are called
uniports.
- Transporters that move multiple solutes are called coupled transporters.
- In coupled transport, the solutes can be transferred either in the same
direction, by symports, or in the opposite direction, by antiports.
- Uniports, symports, and antiports can be used for either passive or active
transport.
Discussion
Figure 12. Two types of glucose

transporters enable gut epithelial
cells to transfer glucose across
the epithelial lining of the gut. In
addition, to keep the
concentration of Na+ in the
cytosol low—and the Na+
electrochemical gradient steep—
Na+ that enters the cell via the
Na+-driven glucose symport
(glucose–Na+ symport) is pumped
out by Na+ pumps in the basal
and lateral plasma membranes, as
indicated. The diet provides
ample Na+ in the gut lumen to
drive the Na+-coupled glucose
symport.
2.6. Ca2+ pumps is another important example of P-type
ATPases keep the cytosolic Ca2+ concentration low
• Ca2+ can bind tightly to a variety of proteins in the cell, altering their
activities.
• An influx of Ca2+ into the cytosol is used by different cells as an
intracellular signal to trigger various cell processes, such as
muscle contraction, fertilization, and nerve cell communication.
• The lower the background concentration of free Ca2+ in the cytosol,
the more sensitive the cell is to an increase in cytosolic Ca2+.
• Eukaryotic cells in general maintain a very low concentration of
free Ca2+ in their cytosol (about 10–4 mM) in the face of a very much
higher extracellular Ca2+ concentration (typically 1–2 mM).
• The huge concentration difference is achieved mainly by means of
ATP-driven Ca2+ pumps in both the plasma membrane and the
endoplasmic reticulum membrane, which actively pump Ca2+ out
of the cytosol.
Figure 13. The Ca2+ pump in the sarcoplasmic reticulum was the first ATP-driven ion
pump to have its three-dimensional structure determined by X-ray crystallography.
When a muscle cell is stimulated, Ca2+ floods into the cytosol from the sarcoplasmic
reticulum—a specialized form of endoplasmic reticulum. The influx of Ca 2+ stimulates
the cell to contract; to recover from the contraction, Ca2+ must be pumped back into the
sarcoplasmic reticulum by this Ca2+ pump. The Ca2+ pump uses ATP to phosphorylate
itself, inducing a series of conformational changes that—when the pump is open to the
lumen of the sarcoplasmic reticulum—eliminate the Ca 2+- binding sites, ejecting the two
Ca2+ ions into the organelle.
2.7. Cystic fibrosis trans-membrane conductance
regulator (CFTR), an special example of ATP-
binding cassette
• CFTR functions is a membrane
protein and ATP-
gated anion channel, increasing
the conductance for
certain anions (e.g. Cl−) to flow
down their electrochemical
gradient  This in contrast to
other ABC proteins which
transduce the free energy of ATP
hydrolysis to the uphill
Figure 14. CFTRs have two transmembrane
movement of substrates  CFTR domains, each linked to a nucleotide-binding
can be considered as a domain (NBD). CFTR also contains another
'broken' ABC transporter that domain called the regulatory domain (R)
leaks when in open conformation (Source: Internet)
• Mutations of the CFTR gene results in cystic fibrosis, a severe autosomal
recessive diseased with three main complications: thickened mucus in the
lungs with frequent respiratory infections, pancreatic insufficiency leading
to malnutrition and diabetes, and male infertility due to the progressive
obstruction and destruction of the developing spermatic cord.
Thin, freely flowing mucus
Figure 15. The mechanism of cystic fibrosis (source: Internet)

Discussion
2.8. DRUG TRANSPORTERS IN HUMAN
- Drug transporters are membrane transporters involved in
the uptake or efflux of drugs by several tissues such as the
intestine, liver, kidney and brain.  They play critical roles in
the absorption, distribution, metabolism, and elimination of
drugs and xenobiotics.
- However, the endogenous functions of many of these drug
transporters are not well understood
- In human, most identified drug transporters to date belong
to two super-families: ABC and SLC.
- About 7% of FDA approved-drugs target multidrug
transporters
Image by Lecturio.
https://www.lecturio.com/concepts/
pharmacokinetics-and-pharmacodynamics/
P-glycoprotein (Pg) as an important
example of drug transporters
• Pg belongs to ABC class
• Pg was first described in tumor cells  reduced the
access of cytotoxic drugs of tumor cells also known as
multidrug resistance protein 1 (MDR1)
• Later, it is also found in a variety of normal tissues with
excretory functions (small intestine, liver and kidney)
and at blood-tissue barriers (blood-brain barrier, blood-
testis barrier and placenta)  is considered as an
important evolutionary adaptation against potentially
toxic substances
Figure 16. Multidrug resistance mediated by P-glycoprotein in cancer
Important clinical significance of Pg include:
• Multidrug resistance in cancer cells: Pg
overexpression is one of the main mechanisms
behind decreased intracellular drug accumulation
and development of multidrug resistance in human
cancers
• Drug interactions: The pharmacokinetics of a drug
may be altered when co-administered with
compounds which inhibit Pg
(colchicine, diltiazem, erythromycin) or induce
(phenobarbital, phenytoin) Pg
3. ION CHANNELS AND THEIR FUNCTIONS
• Channel proteins, or channels form trans-membrane pores that

allow the passive movement of small water-soluble molecules into
or out of the cell or organelle
• Most of the channels in the plasma membrane form narrow, highly
selective pores.
• Exception are a few channels that form relatively large, aqueous
pores: examples are the proteins that form gap junctions between
two adjacent cells and the porins that form pores in the outer
membrane of mitochondria and some bacteria.
• An open ion channel does not need to undergo
conformational changes with each ion it passes  it has
higher rate of transport (1000 times greater than the
fastest rate of transfer known for any transporter).
• Channels cannot couple the ion flow or an energy source
to carry out active transport  most channels simply
make the membrane transiently permeable to selected
inorganic ions, mainly Na+, K+, Ca2+, or Cl–
• Thanks to active transport by pumps, the concentrations
of most ions are far from equilibrium across a cell
membrane. When an ion channel opens, therefore, ions
usually flow through it, moving rapidly down their
electrochemical gradients. This rapid shift of ions changes
the membrane potential.
3.1. Ion channels are ion-selective and gated
• Ion selective: permitting some inorganic ions to pass

but not others. Ion selectivity depends on the diameter
and shape of the ion channel and on the distribution of
the charged amino acids that line it.
• Gated: Ion channels are not continuously open.
A specific stimulus triggers them to switch between a
closed and an open state by a change in their
conformation
Figure 17. Different types of gated ion channels respond to different types of
stimuli. Depending on the type of channel, the probability of gate opening is
controlled by (A) a change in the voltage difference across the membrane, (B) the
binding of a chemical ligand to the extracellular face of a channel, (C) ligand
binding to the intracellular face of a channel, or (D) mechanical stress.
3.2. Membrane potential is governed by the
permeability of a membrane to specific ions
• Changes in membrane potential are the basis of electrical
signaling in many types of cells.
• Such electrical changes are mediated by alterations in the
permeability of membranes to ions.
• In an animal cell that is in an un-stimulated, or “resting”
state, the negative charges on the organic molecules inside
the cell are largely balanced by K+, the predominant
intracellular ion.
• The plasma membrane, however, also contains a set of K +
channels known as K+ leak channels. These channels
randomly flicker between open and closed states no matter
what the conditions are inside or outside the cell; when they
are open, they allow K+ to move freely.
• The resting membrane is chiefly a reflection of the
electrochemical K+ gradient across the plasma membrane,
and it varies between –20 to –200 mV (inside is negative)
Figure 18 .The K+ concentration gradient and K+ leak channels play major parts
in generating the resting membrane potential across the plasma membrane in
animal cells
• When a cell is stimulated, other ion channels in
the plasma membrane open (shown later),
changing the membrane’s permeability to those
ions. Whether the ions enter or leave the cell
depends on the direction of their electrochemical
gradients.
3.3. Action potentials allow rapid long-
distance communication along axons
Figure 19. A typical neuron (nerve cell) has a cell body, a single
axon, and multiple dendrites.
• The fundamental task of a neuron is to receive, integrate, and
transmit signals.
• Neurons carry signals inward from sense organs, such as eyes
and ears, to the central nervous system—the brain and spinal
cord.
• In the central nervous system, neurons signal from one to
another through networks of enormous complexity, allowing
the brain and spinal cord to analyze, interpret, and respond to
the signals coming in from the sense organs.
• In essence, the form of the neuronal signal is always the
same: it consists of changes in the electrical potential across
the neuron’s plasma membrane.
3.4. Voltage-gated cation channels respond
to the membrane action potential
• Voltage-gated ion channels play a major role in propagating
electrical signals along all nerve cell processes
• Voltage-gated ion channels have domains called voltage sensors
that are extremely sensitive to changes in the membrane
potential: changes above a certain threshold value exert
sufficient electrical force on these domains to encourage the
channel to switch from its closed to its open conformation.
• When one type of voltage-gated ion channel opens, the
membrane potential of the cell can change. This in turn can
activate or inactivate other voltage-gated ion channels.
• The circuit, from ion channels  membrane potential → ion
channels, is fundamental to all electrical signaling in cells.
Figure 20. Graph of Action Potential. Voltage is measured across the cell
membrane against time, the action potential begins with depolarization, followed
by repolarization, which goes past the resting potential into hyperpolarization, and
finally the membrane returns to rest.
• When a neuron is stimulated, the membrane potential of the
plasma membrane shifts to a less negative value (that is, toward
zero). If this depolarization is sufficiently large, it will cause
voltage-gated Na+ channels in the membrane to open
transiently at the site  A small amount of Na+ to enter the cell
down its steep electrochemical gradient  The influx of positive
charge depolarizes the membrane further  Opening additional
voltage-gated Na+ channels and causing still further
depolarization.
• This process continues in an explosive, self-amplifying fashion
until, within about a millisecond, the membrane potential in the
local region of the neuron’s plasma membrane has shifted from
its resting value of about –60 mV to about +40 mV.
• The voltage of +40 mV is close to the membrane
potential at which the electrochemical driving force for
movement of Na+ across the membrane is zero
• If the channels continued to respond to the altered
membrane potential, the cell would get stuck with most
of its voltage-gated Na+ channels open
• The cell is saved from this fate because the Na+ channels
have an automatic inactivating mechanism—a kind of
“timer” that causes them to rapidly adopt (within a
millisecond or so) a special inactivated conformation, in
which the channel is closed, even though the membrane
is still depolarized. The Na+ channels remain in this
inactivated state until the membrane potential has
returned to its initial negative value.
Figure 21. A voltage-gated Na+ channel can flip from one conformation to
another, depending on the membrane potential.
• During an action potential, Na+ channels do not act alone. The
depolarized axonal membrane is helped to return to its resting
potential by the opening of voltage-gated K+ channels.
• These also open in response to depolarization, but not as promptly as
the Na+ channels, and they stay open as long as the membrane
remains depolarized.
• As the local depolarization reaches its peak, K+ ions (carrying positive
charge) therefore start to flow out of the cell through these newly
opened K+ channels down their electrochemical gradient, temporarily
unhindered by the negative membrane potential that normally
restrains them in the resting cell.
• The rapid outflow of K+ through the voltage-gated K+ channels brings
the membrane back to its resting state much more quickly than could
be achieved by K+ outflow through the K+ leak channels alone.
• Once it begins, the self-amplifying depolarization of a
small patch of plasma membrane quickly spreads
outward: Na+ flowing in through open Na+ channels
begins to depolarize the neighboring region of the
membrane, which then goes through the same self-
amplifying cycle. In this way, an action potential spreads
outward as a traveling wave from the initial site of
depolarization, eventually reaching the axon terminals
Figure 22. An action potential propagates along the length of an axon.
3.5. Voltage-gated Ca2+ channels in nerve
terminals convert an electrical signal into a
chemical signal and neurotransmitter-gated ion
channels in the postsynaptic membrane convert
the chemical signal back into an electrical signal
• Synapse:
Figure 23
Figure 24. Chemical transmission of a nerve impulse at the synapse. The arrival of
the nerve impulse at the presynaptic terminal stimulates the release of
neurotransmitter into the synaptic gap. The binding of the neurotransmitter to
receptors on the postsynaptic membrane stimulates the regeneration of the action
potential in the postsynaptic neuron
3.6. Neurotransmitters can be excitatory or
inhibitory
• Neurotransmitters can either excite or inhibit a postsynaptic cell, and it is
the character of the receptor that recognizes the neurotransmitter that
determines how the postsynaptic cell will respond.
• The chief receptors for excitatory neurotransmitters, such as
acetylcholine and glutamate, are ligand-gated cation channels. When a
neurotransmitter binds, these channels open to allow an influx of Na+,
which depolarizes the plasma membrane and thus tends to activate the
postsynaptic cell, encouraging it to fire an action potential.
• By contrast, the main receptors for inhibitory neurotransmitters, such as
γ-aminobutyric acid (GABA) and glycine, are ligand-gated Cl– channels.
When neurotransmitters bind, these channels open, increasing the
membrane permeability to Cl–; this change in permeability inhibits the
postsynaptic cell by making its plasma membrane harder to depolarize
Figure 25. Synapses can be excitatory or inhibitory. Excitatory
neurotransmitters activate ion channels that allow the passage of
Na+ and Ca2+ , whereas inhibitory neurotransmitters activate ion
channels that allow the passage of Cl-
3.7. The Complexity of Synaptic Signaling Enables Us to
Think, Act, Learn, and Remember
• An elaborate network of neurons, interconnected by many branching
circuits, performes complex computations, stores memories, and
generates plans for action  Neurons have to do more than merely
generate and relay signals: they must also combine them, interpret
them, and record them  Chemical synapses make these activities
possible.
• A motor neuron in the spinal cord, for example, receives inputs from
hundreds or thousands of other neurons that make synapses on it (Fig.
26)
• Each of the hundreds of types of neurons in the brain has its own
characteristic set of receptors and ion channels that enables the cell to
respond in a particular way to a certain set of inputs and thus to
perform its specialized task.
• Ion channels are thus critical components of the machinery that
enables us to act, think, feel, speak, learn, and remember.
Figure 26. Thousands of synapses form on the cell body and dendrites of a motor
neuron in the spinal cord. (A) Many thousands of nerve terminals synapse on this
neuron, delivering signals from other parts of the animal to control the firing of action
potentials along the neuron’s axon. (B) A rat nerve cell in culture. Its cell body and
dendrites (green) are stained with a fluorescent antibody that recognizes a cytoskeletal
protein. Thousands of axon terminals (red) from other nerve cells (not visible) make
synapses on the cell’s surface; they are stained with a fluorescent antibody that
recognizes a protein in synaptic vesicles, which are located in the nerve terminals
Table 2
3.8. Ion channels as drug targets
• Ion channel modulators are an extremely important drug class, second only to drugs targeting
GPCR
• Ion channels are important drug targets because they play a crucial role in controlling a very
wide spectrum of physiological processes, and because their dysfunction can lead to
pathophysiology
• Ion channels comprise about 16% of current FDA-approved drug targets.
• Major disease areas include the cardiovascular system, the central nervous system, and pain.
Table 3. Some examples of drugs targeting ion channels

• Most psychoactive drugs (i.e. insomnia, anxiety, depression, and Schizophrenia) affect
sneurotransmitter-gated ion channel and synaptic signaling. Ex: fluoxenine
(Prozac)
• The number of distinct types of neurotransmitter receptors is very large, although they fall
into a small number of families. There are, for example, many subtypes of acetylcholine,
glutamate, GABA, glycine, and serotonin receptors; they are usually located on different
neurons and often difffer only subtly in their electrophysiological properties
Figure 27. action
mechanism of SSRI
(example: Fluoxenine
(Prozac))
Fluoxenine is an
antidepressant of the
selective serotonin reuptake
inhibitor (SSRI) class. It
blocks the Na+-driven
symport responsible for the
reuptake of the excitatory
neurotransmitter serotonin,
increasing the amount of
serotonin available in the
synapses that use it. This
drug has changed the lives
of many people who suffer
Source: http://hmphysiology.blogspot.com/2012/10/neurotransmitters.html
from depression—although
Figure 28.
• The four main targets for drug action: receptors, ion channels, carrier
transporters, enzymes.
• In each of these four cases, most drugs are effective because they bind to
particular target proteins.
1. Kích thước và tính tan của các chất quyết định sự khuếch tán trực tiếp của chúng qua
màng phopholipid như thế nào. Nêu vai trò của các protein vận chuyển màng.
2. Nêu được sự khác biệt về nồng độ giữa trong và ngoài màng tế bào của các ion cơ
bản. Giải thích khái niệm điện thế màng.
3. Nêu được 2 nhóm protein vận chuyển màng và các đặc điểm khác biệt cơ bản giữa
chúng
4. So sánh vận chuyển chủ động và vận chuyển bị động; trình bày các cơ chế vận chuyển
có liên quan trong mỗi phương thức này
5. Nêu, so sánh các nhóm transporters và trình bày các ví dụ quan trọng cho từng nhóm
6. Trình bày ngắn gọn về các transporter vận chuyển thuốc nói chung và P-glycoprotein
nói riêng
7. Nêu bản chất của kênh ion, các tính chất cơ bản của kênh ion, phân loại các nhóm
kênh ion tùy vào kích thích gây đóng/mở kênh
8. Nêu được các kênh ion tham gia vào hoạt động điện thế của màng (điện thế nghỉ,
điện thế động, dẫn truyền qua synapse (trước và sau synapse)) và sơ lược về cơ chế
hoạt động của chúng
Self-studying
Chapter 15
INTRACELLULAR COMPARTMENTS AND PROTEIN

TRANSPORT
1. MEMBRANE-ENCLOSED ORGANELLES
2. PROTEIN SORTING
3. VESICULAR TRANSPORT
4. SECRETORY PATHWAYS
5. ENDOCYTIC PATHWAYS
Câu hỏi: Membrane trafficking (vesicle transport) khác biệt cơ bản như thế
nào so với vận chuyển đi qua màng (transport across membrane). Nêu 2
con đường của membrane trafficking và ví dụ cho mỗi con đường
Cell signaling
TS. Nguyễn Minh Nam
Email: nmnam@medvnu.edu.vn
1967 1981 1961
Animal’s senses
concerning the primary physiological and chemical the physical mechanism of

concerning information processing
visual processes in the eye stimulation within the cochlea
in the visual system
Nobel Prize in
Physiology or Medicine
1911 2021 2004
Odorant receptors and the

dioptrics of the eye Receptors for temperature and touch organization of the olfactory system
Content
• GENERAL PRINCIPLES OF CELL SIGNALING
• G-PROTEIN-COUPLED
• ION-CHANNEL-COUPLED RECEPTORS
• ENZYME-COUPLED RECEPTORS
• CELL COMMUNITIES: TISSUES AND CANCER

Cell’s senses
• Individual cells need to sense and respond to their environment.

• Must be able to track down nutrients, tell the difference between
light and dark, and avoid poisons and predators. And if such a cell is
to have any kind of “social life,” it must be able to communicate
with other cells.
Figure 16–1 Yeast cells respond to mating factor. Budding yeast (Saccharomyces
cerevisiae) cells are (A) normally spherical, but (B) when they are exposed to an
appropriate mating factor produced by neighboring yeast cells, they extend a protrusion
toward the source of the factor. (Courtesy of Michael Snyder.)
GENERAL PRINCIPLES OF CELL
SIGNALING
• Information can come in a variety of forms
• Communication frequently involves converting the signals that carry
that information from one form to another.
Figure 16–2 Signal transduction is the process whereby one type of signal is converted into another.
SIGNALING
SIGNALING
Signals Can Act over a Long or Short Range
Proteins
Peptides
Amino acids
Nucleotides
Steroids
Fatty acid derivatives
Gases
Light
Signal molecule
SIGNALING
• cell–cell communicates using extracellular signal molecules called hormones.
• Cells that produce hormones are called endocrine cells

SIGNALING
Figure 16–3 Animal cells use extracellular signal molecules to communicate with one another in various ways.
SIGNALING
Figure 16–3 Animal cells use extracellular signal molecules to communicate with one another in various ways.
SIGNALING
A Limited Set of Extracellular Signals Can Produce a Huge Variety
of Cell Behaviors
SIGNALING
A Limited Set of Extracellular Signals Can Produce a Huge Variety of Cell
Behaviors
Extracellular signal molecules can be divided into two major classes:
• Molecules that are too large or too hydrophilic to cross the plasma membrane of
the target cell. These signal molecules rely on receptors on the surface of the
target cell to relay their message across the plasma membrane
• Molecules that are small enough or hydrophobic enough to pass through the
plasma membrane and into the cytosol of the target cell, where they bind to
intracellular receptor proteins
SIGNALING
of Cell Behaviors
Figure 16–4 Extracellular signal molecules bind either to cell surface receptors or to
intracellular receptors.
SARS-CoV-2 infection pathway
SIGNALING
of Cell Behaviors
Extracellular signal
molecules can change the
behavior of a target cell in a
large variety of ways,
altering its shape, movement,
metabolism, gene expression,
or some combination of
these.
SIGNALING
A Limited Set of Extracellular Signals Can Produce a Huge Variety of Cell Behaviors
• Cell reacts to a signal depends on:

• Intracellular signaling molecules each cell-surface receptor produces
• Molecules alter the activity of effector proteins, which have a direct effect on the behavior of
the target cell.
• This intracellular relay system and the intracellular effector proteins vary from one type
of specialized cell to another, so that different types of cells respond to the same signal
in different ways.
• The extracellular signal molecule alone is not the message: the information conveyed by
the signal depends on how the target cell receives and interprets the signal.
SIGNALING
of Cell Behaviors
Figure 16–5 The same signal molecule can induce different responses in different target cells.
SIGNALING
of Cell Behaviors
Major receptors expressed on the surface

of natural killer (NK) cells
doi.org/10.3390/ijms20020317
SIGNALING
of Cell Behaviors
One signal will often modify the effects of another
One combination of signals might enable a cell to

survive;
another might cause it to divide.
another might drive it to differentiate in some

specialized way; and
In the absence of the proper signals, most

animal cells are programmed to kill themselves
Figure 16–6 An animal cell depends on multiple
extracellular signals.
GENERAL PRINCIPLES OF CELL SIGNALING
A Cell’s Response to a Signal Can Be Fast or Slow
Figure 16–7 Extracellular signals can act slowly or rapidly

SIGNALING
Cell-Surface Receptors Relay Extracellular Signals via Intracellular Signaling Pathways
Figure 16–8 Many extracellular signals activate intracellular signaling pathways to change the
behavior of the target cell.
SIGNALING
Figure 16–9 Intracellular signaling proteins can relay, amplify, integrate,

distribute, and modulate via feedback an incoming signal.
SIGNALING
Figure 16–10 Feedback regulation within an intracellular signaling

pathway can adjust the response to an extracellular signal
Feedback regulation can occur anywhere in the signaling pathway

and can either boost or weaken the response to the signal.
SIGNALING
SIGNALING
Some Intracellular Signaling Proteins Act as Molecular Switches
• Proteins that act as molecular switches fall mostly into one of two
classes.
v Proteins that are activated or inactivated by phosphorylation.
Figure 16–11 Many intracellular signaling

proteins act as molecular switches.
SIGNALING
• Proteins that act as molecular switches fall mostly into one of
two classes.
v Proteins that are activated or inactivated by phosphorylation.
Phosphorylation cascades: one protein
kinase, activated by phosphorylation,
phosphorylates the next protein kinase in
the sequence, and so on, transmitting the
signal onward and, in the process,
amplifying, distributing, and regulating it.
Two main types of protein kinases operate

in intracellular signaling pathways: the
most common are serine/threonine
kinases; others are tyrosine kinases,
SIGNALING
classes.
v Proteins involved in intracellular signaling pathways are GTP-
binding proteins.
• These toggle between an active and an inactive state depending on
whether they have GTP or GDP bound to them, respectively.
Figure 16–11 Many intracellular signaling proteins

act as molecular switches.
SIGNALING
classes.
v Proteins involved in intracellular signaling pathways are GTP-
binding proteins.
• Two main types of GTP-binding proteins participate in intracellular
signaling: trimeric GTP-binding proteins (also called G proteins)—
relay messages from G-protein-coupled receptors and monomeric
GTPases—to help relay their signals.
• These switch proteins are generally aided by two sets of regulatory
proteins that help them bind and hydrolyze GTP: guanine nucleotide
exchange factors (GEFs) activate the switches by promoting the
exchange of GDP for GTP, and GTPase-activating proteins (GAPs)
turn them off by promoting GTP hydrolysis
SIGNALING
Figure 16–12 The activity of monomeric GTPases is

controlled by two types of regulatory proteins
SIGNALING
Cell-Surface Receptors Fall into Three Main Classes
• Ion-channel-coupled receptors change the permeability of the plasma
membrane to selected ions, thereby altering the membrane potential
and, if the conditions are right, producing an electrical current
Erwin Neher
• Born 20 March 1944
• A German biophysicist, specializing in
the field of cell physiology.
• In 1991 he was awarded, along
with Bert Sakmann, the Nobel Prize in
Physiology or Medicine for "their
discoveries concerning the function of
single ion channels in cells".
2014
SIGNALING
• G-protein-coupled receptors activate membrane-bound, trimeric GTP-
binding proteins (G proteins), which then activate (or inhibit) an
enzyme or an ion channel in the plasma membrane, initiating an
intracellular signaling cascade
SIGNALING
• Enzyme-coupled receptors either act as enzymes or associate with
enzymes inside the cell; when stimulated, the enzymes can activate a
wide variety of intracellular signaling pathways
SIGNALING
Ion-Channel-Coupled Receptors Convert Chemical Signals into Electrical Ones
Figure 12–41 A chemical signal is converted into an electrical signal by postsynaptic

transmitter-gated ion channels at a synapse.
SIGNALING
• They transduce a chemical signal, in the form of a pulse of secreted
neurotransmitter molecules delivered to a target cell, directly into an electrical
signal, in the form of a change in voltage across the target cell’s plasma
membrane.
SIGNALING
Copyright 2009 John Wiley & Sons, Inc.

G-PROTEIN-COUPLED RECEPTORS
• The receptors that accept signal transduction are:
v G protein-coupled receptors (GPCRs) are a huge family of receptors. These

receptors translate the binding of extracellular signaling molecules into the
activation of GTP-binding proteins
v Receptor protein-tyrosine kinases (RTKs) translate the presence of extracellular

messenger molecules into changes inside the cell
v Ligand-gated channels conduct a flow of ions across the plasma membrane.

These can function as receptors for neurotransmitters
v Steroid hormone receptors function as ligand-regulated transcription factors
v Other types of receptors act by unique mechanisms. For example, the B- and
T-cell receptors
• Because GPCRs are involved in such a large variety of cell processes,

they are an attractive target for the development of drugs to treat
many disorders. About one-third of all drugs used today work through
GPCRs.
Figure 16–14 All GPCRs possess a similar structure

Brian K. Kobilka
• Born: 30 May 1955, USA

• The Nobel Prize in Chemistry 2012
• "for studies of G-protein-coupled
receptors.
2014
Stimulation of GPCRs Activates G-Protein Subunits
• All of these G proteins have a similar general structure and operate in
a similar way. They are composed of three protein subunits—α, β, and
γ—two of which are tethered to the plasma membrane by short lipid
tails.
Figure 16–15 An activated GPCR plasma

membrane activates G proteins by encouraging
the α subunit to expel its GDP and pick up GTP.
Figure 16–16 The G protein α subunit

switches itself off by hydrolyzing its
bound GTP to GDP.
Some G Proteins Directly Regulate Ion Channels
slows the heart rate
Figure 16–17 A Gi protein directly couples receptor activation to the opening of

K+ channels in the plasma membrane of heart pacemaker cell
Many G Proteins Activate Membrane-bound Enzymes That Produce Small
Messenger Molecules
Figure 16–18 Enzymes activated by G

proteins increase the concentrations of
small intracellular signaling molecules
The Cyclic AMP Signaling Pathway Can Activate Enzymes and Turn On Genes
Activated G protein α subunit

switches on the adenylyl cyclase,
causing a dramatic and sudden
increase in the synthesis of cyclic
AMP from ATP.
To help terminate the signal, a
second enzyme, called cyclic AMP
phosphodiesterase, rapidly
converts cyclic AMP to ordinary
AMP
Figure 16–19 Cyclic AMP is synthesized by adenylyl

cyclase and degraded by cyclic AMP phosphodiesterase.
• Cyclic AMP exerts most of its effects by activating the enzyme cyclic-AMP-
dependent protein kinase (PKA).
• This enzyme is normally held inactive in a complex with a regulatory protein.

The binding of cyclic AMP to the regulatory protein forces a conformational
change that releases the inhibition and unleashes the active kinase.
• Activated PKA then catalyzes the phosphorylation of particular serines or

threonines on specific intracellular proteins, thus altering the activity of these
target proteins.
Figure 16–21 Epinephrine stimulates

glycogen breakdown in skeletal muscle
cells.
Figure 16–22 A rise in intracellular cyclic

AMP can activate gene transcription.
Some Bacterial Toxins Cause Disease by Altering the Activity of G Proteins
• Cholera toxin multimeric protein complex secreted by the bacterium
Vibrio cholerae.
• Modifies the α subunit of a G protein called Gs
• Stimulates the enzyme adenylyl cyclase
• Prevents Gs from hydrolyzing its bound GTP
• locking the G protein in an active state
• continuously stimulates adenylyl cyclase.
• prolonged and excessive outflow of Cl– and water into the gut
• resulting in catastrophic diarrhea and dehydration
• leads to death unless urgent steps are taken to replace the lost water and ions.
Some Bacterial Toxins Cause Disease by Altering the Activity of G
Proteins
• A similar situation occurs in whooping cough (pertussis)

• disease-causing bacterium colonizes the lung
• Produces a protein called pertussis toxin.
• This protein alters the α subunit of a different type of G
protein, called Gi
• inhibits adenylyl cyclase.
• disables the G protein by locking it into its inactive GDP-
bound state
• results in stimulates coughing.
• help the disease-causing bacteria move from host to host.
The Inositol Phospholipid Pathway Triggers a Rise in Intracellular Ca2+
The Inositol Phospholipid Pathway Triggers a Rise in Intracellular Ca2+
lipid
Water-soluble sugar phosphate
Figure 16–23 Phospholipase C activates two signaling pathways

ENZYME-COUPLED RECEPTORS
Activated RTKs Recruit a Complex of Intracellular Signaling Proteins
• Receptor tyrosine kinases (RTKs) are the largest class of enzyme-coupled
receptors consists of receptors with a cytoplasmic domain that functions as a
tyrosine kinase.
Figure 16–29 Activation of an RTK stimulates the assembly of an intracellular

signaling complex.
Most RTKs Activate the Monomeric GTPase Ras
• Ras—a small GTP-binding protein that is bound by a lipid tail to the cytosolic
face of the plasma membrane
Figure 16–30 RTKs activate Ras.

Most RTKs Activate the Monomeric GTPase Ras
Figure 16–31 Ras activates a MAP-kinase signaling module.

RTKs Activate PI 3-Kinase to Produce Lipid Docking Sites in the Plasma
Membrane
Figure 16–32 Some RTKs activate the PI-3-kinase–Akt signaling pathway

Membrane
Figure 16–33 Activated Akt promotes cell survival.

Membrane
Figure 16–34 Akt stimulates cells to grow

in size by activating the serine/threonine
kinase Tor.
Membrane
Figure 16–35 Both GPCRs and RTKs activate multiple intracellular signaling pathways.
SIGNALING
of Cell Behaviors
Figure 16–4 Extracellular signal molecules bind either to cell surface receptors or to
intracellular receptors.
Figure 16–41 The steroid hormone cortisol acts by activating a transcription regulator
Protein Kinase Networks Integrate Information to Control Complex Cell
Behaviors
Figure 16–43 Intracellular signaling proteins serve to integrate incoming signals.

Overview of Interlinked Cellular Signaling Pathways Involved in the Proliferation and
Progression of Colorectal Cancer
https://doi.org/10.7314/APJCP.2012.13.4.1705
Role of aberrant cell signaling in cancer drug resistance
https://doi.org/10.1007/s11033-019-04958-6
Cell Communities:
Tissues and Cancer
Cell Communities: Tissues, Stem Cells,
and Cancer
•Most of the cells in multicellular organisms are
organized into cooperative assemblies called tissues
•Tissues are organized into organs
Cell Communities: Tissues, Stem Cells,
and Cancer
•Animal tissue requires blood vessels, nerves, and
other components formed from a variety of
specialized cell types.
•Cells die and have to be replaced with new cells of
the right type, in the right places, and in the right
numbers
EXTRACELLULAR MATRIX AND
CONNECTIVE TISSUES
The Four Primary Tissue Types

EXTRACELLULAR MATRIX AND
CONNECTIVE TISSUES
•Animal connective tissues are enormously varied.
•They can be tough and flexible like tendons or the
dermis of the skin; hard and dense like bone;
resilient and shock-absorbing like cartilage; or soft
and transparent like the jelly that fills the interior of
the eye.
EXTRACELLULAR MATRIX AND CONNECTIVE TISSUES
https://doi.org/10.1111/febs.14818
What is cancer
https://www.aacrfoundation.org/Pages/what-is-cancer.aspx
Cause of Cause of Cancer
• Mutations in genes that regulate:
• Cell Division
• Cell Growth
• Cell Death
The biology and treatment of cancer : understanding cancer / Arthur B. Pardee, Gary S. Stein.
https://www.cusabio.com/
Extrinsic signaling and gain-of-function
p53 mutants
DOI: 10.1016/j.jmb.2017.03.030
Cell cycle checkpoints
http://www.slk-art.com/new-page
Immune system's response to cancer
Doi: 10.1016/j.bbcan.2016.02.002
How Cancer Is Diagnosed?
• Biopsy of the tumor

• Blood tests (which look for chemicals such as tumormarkers)
• Bone marrow biopsy (for lymphoma or leukemia)
• Chest x-ray
• Complete blood count
• CT scan
• Liver function tests
• MRI scan
• Pap test
Distinguishing early diagnosis from screening
Cancer treatment
http://giveityourall.net/treatment-options/
Why current therapies fail
• Tumor cells are genetically unstable
• Tumors can become drug resistant
• Tumors can remain dormant for years
• Tumor metastases are hard to find and difficult to access
• Current therapies are toxic to the patient

The paracrine model of cancer drug resistance
Doi: 10.1016/j.bbcan.2016.03.005
Cancer is not a single disease
https://www.delveinsight.com/
Cancers are clonal
•All the cells in a tumor originate from a single

ancestral cell.
•But, not all cells in a tumor have the same genotype
because cancer cells are genetically unstable.
•Variation gives rise to selection.
•Clonal selection of variant progeny with the most
robust growth properties play major contributing
roles.
Cancer genomic heterogeneity
DOI:10.1093/pcmedi/pby007
Before initiation After 15 weeks After 23 weeks
of PLX4032 of therapy of therapy
Doi: 10.1200/JCO.2010.33.2312
Precision medicine
• Right drug, right dose, right patient, right time.
Precision medicine
https://genxpro.net
5 Curable Cancers
• Prostate Cancer
People alive 5 years after diagnosis: About 99%
• Thyroid Cancer
People alive 5 years after diagnosis: about 98% (depending on tissue type)
• Testicular Cancer
People alive 5 years after a diagnosis: 95.1%
• Melanoma
People alive 5 years after a diagnosis: 91.7%
• Breast Cancer -- Early Stage
People alive 5 years after a diagnosis: early stages of 0 and 1 - 99% to 100%
Câu hỏi ôn tập
• 1. Tín hiệu tế bào là gì? Con đường dẫn truyền tín hiệu được bắt đầu như thế
nào? Nêu ví dụ các loại phân tử tín hiệu ngoại bào.
• 2. Nêu các thụ thể trong dẫn truyền tín hiệu.
• 3. Mô tả các loại tín hiệu gây ra bởi các phân tử tín hiệu ngoại bào và cách
thức hoạt động của chúng.
• 4. Nêu sự khác biệt giữa G Protein Coupled Receptors và Receptor Tyrosine
Kinases.
• 5. Vai trò của Ras trong con đường tín hiệu là gì? Ras có ảnh hưởng như thế
nào đến hoạt tính của Ras-GAP?
• 6. Extracellular matrix là gì? Vai trò của Extracellular matrix.
• 7. Cancer được hình thành như thế nào?
• 8. Con đường tín hiệu trong tế bào ung thư thay đổi như thế nào so với tế bào
thường? Ý nghĩa của nó trong việc chẩn đoán và điều trị ung thư.
Cell cycle, cell division
and cell death
TS. Nguyễn Minh Nam
Email: nmnam@medvnu.edu.vn
• How many cells an adult human body has.
• 60–100 trillion
• Where those cells came from.
• a single fertilized cell
• means that all the cells in their body are the same?
• No, they have differentiated
• If cells in an embryo divide rapidly, what stops
them from continuing to divide.
• internal, external regulation
• How does a cell produce a new cell?
https://www.aatbio.com/
Content
• OVERVIEW OF THE CELL CYCLE
• THE CELL-CYCLE CONTROL SYSTEM
• CELL DIVISION
• CONTROL OF CELL NUMBERS AND CELL SIZE
• THE CHROMOSOMAL BASIS OF INHERITANCE
OVERVIEW OF THE CELL CYCLE
• The cell cycle, or cell-division cycle, is the series of
events that take place in a cell that cause it to divide
into two daughter cells
Figure 18−1 Cells reproduce by

duplicating their contents and dividing in
two in a process called the cell cycle
The Eukaryotic Cell Cycle Usually Includes Four Phases
Figure 18–2 The eukaryotic cell cycle usually occurs in four phases
A Cell-Cycle Control System Triggers the Major Processes of the Cell Cycle
• cell-cycle control system
Figure 18−3 The cell-cycle control system

ensures that key processes in the cycle
occur in the proper sequence.
Cell-Cycle Control Is Similar in All Eukaryotes
• Because of this similarity, biologists can study the cell cycle
and its regulation in a variety of organisms and use the
findings from all of them to assemble a unified picture of
how the cycle works.
• Many discoveries about the cell cycle have come from a
systematic search for mutations that inactivate essential
components of the cell-cycle control system in yeasts.
A Cell-Cycle Control System Triggers the Major Processes of the Cell Cycle
THE CELL-CYCLE CONTROL SYSTEM
The Cell-Cycle Control System Depends on Cyclically
Activated Protein Kinases Called Cdks
• Governs the cell-cycle machinery by cyclically activating
and then inactivating the key proteins and protein
complexes that initiate or regulate DNA replication, mitosis,
and cytokinesis.
• This regulation is carried out largely through the
phosphorylation and dephosphorylation of proteins
involved in these essential processes.
• Switching these kinases on and off at the appropriate times is partly
the responsibility of another set of proteins in the control system—the
cyclins.
• Cyclins have no enzymatic activity themselves, but they must bind to

the cell-cycle kinases before the kinases can become enzymatically
active.
• The kinases of the cell-cycle control system are therefore known as

cyclin-dependent protein kinases, or Cdks.
• Cyclins are so-named because, unlike the Cdks, their concentrations

vary in a cyclical fashion during the cell cycle.
Sir Richard Timothy Hunt
• born 19 February 1943
• a British biochemist and

molecular physiologist.
• awarded the 2001 Nobel Prize in

Physiology or Medicine with
Paul Nurse and Leland H.
Hartwell for their discoveries of
protein molecules that control 2013
the division of cells. working with women was troublesome

because “they fall in love with you and
when you criticize them, they cry,”
Figure 18−4 Progression through the cell cycle depends on cyclindependent protein kinases (Cdks).
Figure 18−5 The accumulation of cyclins helps regulate the activity of Cdks.
Different Cyclin–Cdk Complexes Trigger Different Steps in
the Cell Cycle
• There are several types of cyclins and several types of Cdks
involved in cell-cycle control.
• Different cyclin–Cdk complexes trigger different steps of the
cell cycle.
Different Cyclin–Cdk Complexes Trigger Different Steps
in the Cell Cycle
Cyclin Concentrations Are Regulated by Transcription
and by Proteolysis
doi: 10.1242/dev.091744
Cyclin Concentrations Are Regulated by Transcription
Roger D. Kornberg
• Born: 24 April 1947, USA
• The Nobel Prize in
Chemistry 2006
• "for his studies of the
molecular basis of
eukaryotic transcription."
2011
Ada E. Yonath
• Born: 22 June 1939,
Jerusalem, British
Mandate of Palestine
(now Israel) 2016
Chemistry 2009
• "for studies of the
structure and function of
the ribosome."
2010
Cyclin Concentrations Are Regulated by Proteolysis
Figure 18−9 The activity of some Cdks is regulated by cyclin degradation.

Aaron Ciechanover
• Born: 1 October 1947,
British Protectorate of
Palestine (now Israel)
Chemistry 2004
• "for the discovery of
ubiquitin-mediated
protein degradation"
2015
The Activity of Cyclin–Cdk Complexes Depends on
Phosphorylation and Dephosphorylation
Figure 18−10 For M-Cdk to be active,

inhibitory phosphates must be removed.
Cdk Activity Can Be Blocked by Cdk Inhibitor Proteins
Figure 18−11 The activity of a Cdk can be

blocked by the binding of a Cdk inhibitor.
The Cell-Cycle Control System Can Pause the Cycle in
Various Ways
Figure 18−12 The cell-cycle control system uses various mechanisms to pause the cycle at specific transition points
G1 PHASE
G1 PHASE
Figure 18−13 The transition from G1 to S phase offers the cell a crossroad
G1 PHASE
• Mitogens Promote the Production of the Cyclins That
Stimulate Cell Division
Figure 18−14 One way in which mitogens

stimulate cell proliferation is by inhibiting
the Rb protein.
G1 PHASE
Figure 18−15 DNA damage can arrest the

cell cycle in G1.
G1 PHASE
• Cells Can Delay Division for Prolonged Periods by
Entering Specialized Nondividing States
• G0 phase:
• None-dividing, differentiated state
• Most human cells in G0 phase
S PHASE
• S-Cdk Initiates DNA Replication and Blocks Re-Replication
Figure 18−16 The initiation of DNA

replication takes place in two steps.
M PHASE
• M-Cdk Drives Entry into Mitosis
Figure 18−17 Activated M-Cdk indirectly activates more

M-Cdk, creating a positive feedback loop.
M PHASE
MITOSIS
• Mitosis is a process of nuclear division in which the replicated

DNA molecules of each chromosome are faithfully segregated
into two nuclei. Mitosis can take place in either haploid (đơn
bội) or diploid (lưỡng bội) cells
• Mitosis is usually accompanied by cytokinesis, a process by

which a dividing cell splits in two, partitioning the cytoplasm
into two cellular packages
MITOSIS
Centrosomes Duplicate to Help Form the Two Poles of the
Mitotic Spindle
Figure 18−20 Sister chromatids separate

at the beginning of anaphase
MITOSIS
MITOSIS
MITOSIS
MITOSIS
Meiosis
Life cannot exist without cellular death
Types of cell death
Cell death can occur via several processes (about 11 type):
1. Apoptosis
2. Necrosis
3. Autophagy
4. Entosis
5. Oncosis
6. Pyroptosis
7. Excitotoxicity
.
.
.
11.
ØThe word ‘‘apoptosis’’ comes from the ancient
Greek, meaning the: ‘‘falling of petals from a
flower’’ or ‘‘of leaves from a tree in autumn’’
Sydney Brenner
• Born: 13 January 1927, South
Africa.
• Died: 5 April 2019,
Singapore
Physiology or Medicine 2002
"for their discoveries
concerning genetic regulation
of organ development and
programmed cell death"
2013
Yoshinori Ohsumi
• Born: 9 February 1945, Japan

Physiology or Medicine 2016
• "for his discoveries of

mechanisms for autophagy”
2017
• Apoptosis is the physiological cell death which
unwanted or useless cells are eliminated during
development and other normal biological processes.
• Necrosis is the pathological cell death which occurs
when cells are exposed to a serious physical or
chemical insult (hypoxia, hyperthermia, ischemia).
• Autophagy is the body’s way of cleaning out
damaged cells, in order to regenerate newer,
healthier cells
CONTROL OF CELL NUMBERS AND
CELL SIZE
Three Pathways of Cell Death DOI: 10.1056/NEJMra0901217

CELL SIZE
Apoptosis Helps Regulate Animal Cell Numbers
Figure 18−36 Apoptosis in the developing mouse paw sculpts the digits
CELL SIZE
Apoptosis Helps Regulate Animal Cell Numbers
Figure 18−37 As a tadpole changes into a frog, the cells in its tail are
induced to undergo apoptosis.
CELL SIZE
Extrinsic and intrinsic apoptotic signalling pathways

THE CHROMOSOMAL BASIS
OF INHERITANCE
Mendelian inheritance has its physical basis in the
behavior of chromosomes
• Mendel’s “hereditary factors” were genes
• Today we know that genes are located on
chromosomes
• The behavior of chromosomes during meiosis can
account for Mendel’s laws of segregation and
independent assortment
Mendel's laws of inheritance (with modification)
Law Definition
During gamete formation, the alleles
for each gene segregate from each
Law of segregation
other so that each gamete carries
only one allele for each gene.
Genes for different traits can
Law of independent
segregate independently during the
assortment
formation of gametes.
Some alleles are dominant while
others are recessive; an organism
Law of dominance with at least one dominant allele
will display the effect of the
dominant allele.
Mendel’s Garden Pea Plant Experiment
P Generation Yellow-round Green-wrinkled
seeds (YYRR) seeds (yyrr)
Y ry
´
R R r
Y y
Meiosis
Fertilization
R Y y r
Gametes
All F1 plants produce

yellow-round seeds (YyRr).
F1 Generation
R R
y y
r r
Y Y
Meiosis
LAW OF SEGREGATION LAW OF INDEPENDENT
The two alleles for each r r R ASSORTMENT Alleles of genes
R
gene separate during on nonhomologous chromosomes
gamete formation. Metaphase I assort independently during
gamete formation.
Y y Y y
1 1
R r r R
Anaphase I
Y y Y y
R r r R
2 2
Y y Metaphase II Y y
Y y Y
Y y Y y y
Gametes
R R r r r r R R
1 /4 YR 1 /4 yr 1 /4 Yr 1 /4 yR
F2 Generation An F1 ´ F1 cross-fertilization
3 Fertilization recombines 3 Fertilization results in the
the R and r alleles at 9:3:3:1 phenotypic ratio
random. 9 :3 :3 :1 in the F2 generation.
P Generation Yellow-round Green-wrinkled
seeds (YYRR) seeds (yyrr)
Y y
´ r
R R r
Y y
Meiosis
Fertilization
R Y y r
Gametes
All F1 plants produce
yellow-round seeds (YyRr).
F1 Generation
R R
y y
r r
Y Y
LAW OF INDEPENDENT
LAW OF SEGREGATION Meiosis
ASSORTMENT Alleles of
The two alleles for each R r r R genes on nonhomologous
gene separate during chromosomes assort
gamete formation. Metaphase I independently during gamete
Y y Y y formation.
1 1
R r r R
Anaphase I
Y y Y y
R r r R
Metaphase
2 II 2
Y y Y y
Y y Y
Y y Y y y
Gametes
R R r r r r R R
1
1
/4 YR 1/
4 yr 1
/4 Yr /4 yR
LAW OF SEGREGATION LAW OF INDEPENDENT
ASSORTMENT
F2 Generation
An F1 ´ F1 cross-fertilization
3 Fertilization 3 Fertilization results

recombines the in the 9:3:3:1
R and r alleles 9 :3 :3 :1 phenotypic ratio in
at random. the F2 generation.
Morgan’s Experimental Evidence
• The first solid evidence associating a specific gene
with a specific chromosome came from Thomas Hunt
Morgan, an embryologist
• Morgan’s experiments with fruit flies provided
convincing evidence that chromosomes are the
location of Mendel’s heritable factors
Morgan’s Choice of Experimental
Organism
• Several characteristics make fruit flies a convenient
organism for genetic studies
• They produce many offspring
• A generation can be bred every two weeks
• They have only four pairs of chromosomes
• Morgan noted wild type, or normal, phenotypes that
were common in the fly populations
• Traits alternative to the wild type are called mutant
phenotypes
Correlating Behavior of a Gene’s Alleles
with Behavior of a Chromosome Pair
• In one experiment, Morgan mated male flies with
white eyes (mutant) with female flies with red eyes
(wild type)
• The F1 generation all had red eyes
• The F2 generation showed the 3:1 red : white eye ratio,
but only males had white eyes
• Morgan determined that the white-eyed mutant allele
must be located on the X chromosome
• Morgan’s finding supported the chromosome theory
of inheritance
EXPERIMENT
P
Generation
F1 All offspring
Generation had red eyes.
RESULTS
F2
Generation
CONCLUSION
P w+ w
X X
Generation X Y
w+
w
Sperm
Eggs
F1 w+
w+ w+
Generation
w
w+
Sperm
Eggs
w+ w+
w+
F2
Generation w+
w w
w
w+
EXPERIMENT
P
Generation
F1 All offspring
Generation had red eyes.
RESULTS
F2
Generation
CONCLUSION
P w+ w
X X
Generation X Y
w+
w
Sperm
Eggs
F1 w+ w+
w+
Generation
w
w+
Sperm
Eggs
w+ w+
w+
F2
Generation w+
w w
w
w+
The Chromosomal Basis of Sex
• In humans and other mammals, there are
two varieties of sex chromosomes: a larger
X chromosome and a smaller Y
chromosome
• Only the ends of the Y chromosome have
regions that are homologous with
corresponding regions of the X
chromosome
• The SRY gene on the Y chromosome codes
for a protein that directs the development
of male anatomical features
© 2011 Pearson Education, Inc.

• A gene that is located on either sex chromosome is
called a sex-linked gene
• Genes on the Y chromosome are called Y-linked genes;
there are few of these
• Genes on the X chromosome are called X-linked
genes
Inheritance of X-Linked Genes
• X chromosomes have genes for many characters
unrelated to sex, whereas the Y chromosome mainly
encodes genes related to sex determination
• X-linked genes follow specific patterns of inheritance
• For a recessive X-linked trait to be expressed
• A female needs two copies of the allele
(homozygous)
• A male needs only one copy of the allele
(hemizygous)
• X-linked recessive disorders are much more common in
males than in females
• Some disorders caused by recessive alleles on the X
chromosome in humans
• Color blindness (mostly X-linked)
• Duchenne muscular dystrophy
• Hemophilia
X Inactivation in Female Mammals
• In mammalian females, one of the two X
chromosomes in each cell is randomly inactivated
during embryonic development
• The inactive X condenses into a Barr body
• If a female is heterozygous for a particular gene
located on the X chromosome, she will be a mosaic
for that character
X chromosomes
Allele for
orange fur
Early embryo:
Allele for
black fur
Cell division and

X chromosome
Two cell inactivation
populations
in adult cat: Active X
Inactive X
Active X
Black fur Orange fur

Linked genes tend to be inherited together because
they are located near each other on the same
chromosome
• Each chromosome has hundreds or thousands of

genes (except the Y chromosome)
• Genes located on the same chromosome that tend to
be inherited together are called linked genes
How Linkage Affects Inheritance
• Morgan did other experiments with fruit flies to see
how linkage affects inheritance of two characters
• Morgan crossed flies that differed in traits of body
color and wing size
EXPERIMENT P Generation (homozygous)
Double mutant
Wild type (black body,
(gray body, normal wings) vestigial wings)
b+ b+ vg+ vg+ b b vg vg
F1 dihybrid Double mutant

(wild type) TESTCROSS
b+ b vg+ vg b b vg vg
Testcross
offspring Eggs b+ vg+ b vg b+ vg b vg+
Wild type Black- Gray- Black-

(gray-normal) vestigial vestigial normal
b vg
Sperm
b+ b vg+ vg b b vg vg b+ b vg vg b b vg+ vg
PREDICTED RATIOS
If genes are located on different chromosomes: 1 : 1 : 1 : 1
If genes are located on the same chromosome and

parental alleles are always inherited together: 1 : 1 : 0 : 0
RESULTS 965 : 944 : 206 : 185

• Morgan found that body color and wing size are
usually inherited together in specific combinations
(parental phenotypes)
• He noted that these genes do not assort
independently, and reasoned that they were on the
same chromosome
F1 dihybrid female b+ vg+ b vg
and homozygous
recessive male b vg b vg
in testcross
b+ vg+ b vg
Most offspring or
b vg b vg
• However, nonparental phenotypes were also produced
• Understanding this result involves exploring genetic
recombination, the production of offspring with
combinations of traits differing from either parent
Recombination of Linked Genes: Crossing
Over
• Morgan discovered that genes can be linked, but the
linkage was incomplete, because some recombinant
phenotypes were observed
• He proposed that some process must occasionally
break the physical connection between genes on the
same chromosome
• That mechanism was the crossing over of
homologous chromosomes
Figure 15.10
Testcross Gray body, normal wings Black body, vestigial wings
parents (F1 dihybrid) (double mutant)
b+ vg+ b vg
b vg b vg
Replication Replication
of chromosomes of chromosomes
b+ vg+ b vg
b+ vg+ b vg
b vg b vg
b vg b vg
Meiosis I
b+ vg+
Meiosis I and II
b+ vg
b vg+
b vg
Meiosis II
Recombinant
chromosomes
b+vg+ b vg b+ vg b vg+
Eggs
Testcross 965 944 206 185

offspring Wild type Black- Gray- Black-
(gray-normal) vestigial vestigial normal b vg
b+ vg+ b vg b+ vg b vg+
b vg b vg b vg b vg Sperm
Parental-type offspring Recombinant offspring
Recombination = 391 recombinants ´

frequency 100 = 17%
2,300 total offspring
Figure 15.10a
Testcross Gray body, normal wings Black body, vestigial wings
parents (F1 dihybrid) (double mutant)
b+ vg+ b vg
b vg b vg
Replication Replication
of chromosomes of chromosomes
b+ vg+ b vg
b+ vg+ b vg
b vg b vg
b vg b vg
Meiosis I
b+ vg+
Meiosis I and II
b+ vg
b vg+
b vg
Meiosis II
Recombinant
chromosomes
b+vg+ b vg b+ vg b vg+ b vg
Eggs Sperm
Recombinant
chromosomes
b+vg+ b vg b+ vg b vg+
Eggs
Testcross 965 944 206 185

offspring Wild type Black- Gray- Black-
(gray-normal) vestigial vestigial normal b vg
b+ vg+ b vg b+ vg b vg+
b vg b vg b vg b vg Sperm
Parental-type offspring Recombinant offspring
Recombination 391 recombinants ´ 100 = 17%

frequency =
2,300 total offspring
CELL and MOLECULAR BIOLOGY
Molecular Biology: Unit 1
NUCLEIC ACID STRUCTURE AND

DNA REPLICATION

Email: hangdo009@gmail.com
REFERENCES:
• Biochemistry and Medical Genetics – Kaplan USMLE Lecture
Notes – 2021, Section I: Chapter 1 and 2
• Essential Cell Biology (5th Edition, 2019) written by Albert,
Bray, Hopkin, et al, Chapter 5 and 6
MAIN CONTENTS
1. CENTRAL DOGMA OF MOLECULAR BIOLOGY
2. STRUCTURE OF NUCLEIC ACID
3. ORGANIZATION OF DNA
4. DNA REPLICATION
5. DNA REPAIR
6. HUMAN GENOME AND PHARMACOGENETICS/GENOMICS

1/ CENTRAL DOGMA OF MOLECULAR BIOLOGY
Gene expression
“Information cannot be
transferred back from
protein to either protein
or nucleic acid”
"DNA makes RNA

and RNA makes
protein”
• Types of nucleic acid differ

Reverse Transcriptase: • Lengths of nucleic acid differ
Comparison of
• Retroviruses, most notably HIV
Replication and • Enzymes involves differ
• Eukaryotic cells : telomerase (hTRT),
Transcription • Phases of cell cycle differ
retrotransposons
The cell cycle in Eukaryote
Low level of transcription
Non-dividing cells
(Resting cells)
Transcription and Replication

Translation
Signal = growth factors (from
neighbors)
Many chemotherapeutic agents target specific phases
of the cell cycle.
• S phase: 5-flurouracil Methotrexate
• G2 phase: Bleomycin
• M phase: Paclitaxel Vincristine Vinblastine
• Non cell-cycle specific: Cyclophosphamide Cisplatin

The genetic information flow in prokaryote and eukaryote (Molecular
Biology of the Cell, 4th Edition)
Comparison of Gene Expression and DNA replication
Differs between tissues Same in all tissues

2/ STRUCTURE OF NUCLEIC ACID
2.1/ Structure of Bases in Nucleic Acids
“Pure As Gold” “C U T”
Deamination Deamination
+CH3
DNA DNA DNA DNA

RNA RNA RNA RNA
Nucleoside = Nitrogen Base + Sugar
Nucleotide = Nitrogen Base + Sugar + Phosphate
Nucleosides
Nitrogen
base
Sugar
Nucleotides
High-Energy in a
Nucleotide = Nitrogen Base + Sugar + P Nucleoside Triphosphate
Differences in DNA vs. RNA:

• Ribose type
• Pyrimidine type
Nomenclature of Important Bases,
Nucleosides, and Nucleotides
2.2/ Structure of double stranded DNA
Rosalind Franklin X-ray

crystallography of
DNA
James Watson and Francis Crick., 1953
“It has not escaped our notice that the specific pairing we have postulated immediately
suggests a possible copying mechanism for the genetic material.”Watson & Crick
Chargaff’s Rules (in Example 1/
the late 1940s.)
If a sample of dsDNA has 30% A.
What is the %C ?
Ans: 20%
Explain:
If 30% A, then also 30% T
%A + %T = 60%  %G + %C = 40%
G=C  both are 20%
Example 2/ Suppose a sample of DNA has 10% A and 50% G. What is the significance?
Ans: Single-stranded nucleic acid
Key features of dsDNA:
1. Antiparallel Nucleotide
HB
• Deoxyribose-P on outside PDE
• Bases on inside
Nucleotide
2. Complementary (A:T, G:C)
 A equals T, G equals C
Nucleotide
5’ TCAG 3’
5’ TpCpApG 3’
3’ GACT 5’ Nucleotide
TACG ???
In many eukaryotes, genes include an
excess of interspersed, noncoding DNA.
Presented here is the nucleotide sequence

of the human β-globin gene. This gene
carries the information that specifies the
amino acid sequence of one of the two
types of subunits found in hemoglobin, a
protein that carries oxygen in the blood.
Only the sequence of the coding strand is

shown here; the noncoding strand of the
double helix carries the complementary
sequence. Starting from its 5′ end, such a
sequence is read from left to right, like any
piece of English text.
The segments of the DNA sequence that

encode the amino acid sequence of β-globin
are highlighted in yellow.
Watson-Crick model = B-DNA:
• RT-handed helix
• 10 bases = 34 Å /turn of helix
• 23.7 Å wide
- Double-stranded DNA is the

major form of genetic material (in
nucleus, mitochondria, and plasmid)
- Exception: viral genome

• PCR
DNA
• Hybridization
Denaturation
3/ ORGANIZATION OF DNA
Prokaryotic versus Eukaryotic Genome
PROKARYOTE GENOME EUKARYOTE GENOME
They are small in size They are larger than prokaryotic
genome (~ 1000X)
Contains single circular chromosome Contains multiple linear chromosome
They are haploid They are diploid
DNA is not associated with histones DNA is associated with histones
They are condensed in nucleoid via They are condensed in membrane

DNA supercoiling bound nucleus via histones
DNA Packaging in Eukaryotic Cell
• Chromatine = DNA
+ Protein
• Nucleosome =
DNA + Histone
octamer
DNA Packaging in Eukaryotic Cell
Source: https://slideplayer.com/slide/12237275/
• DNA is still packed tightly but 20 times less condensed
An Interphase Nucleus than mitotic DNA
• Contain Both Condensed and More Extended Forms
of Chromatin
DNA Methylation:
• Impede the binding of
transcriptional proteins
• Recruit proteins that inhibit
transcription
 Often tnactivates transcription
Histone acetylation/Histone
phosphorylation:
• Lessens overall positive charge
• Lessens interaction with DNA
 Often activates transcription
Heterochromatin: dark-staining Euchromatin: light-staning:

• Active genes
Changes in chromatin structure
• Inactive genes, Xx: Barr
bodies • In apoptosis: euchromatine can be inherited  Epigenetic
• Contain few genes being cut first inheritance
The pattern of modification of histone tails can determine how a stretch of chromatin is handled by the cell.
(A) Schematic drawing showing the positions of the histone tails that extend from each nucleosome core particle. Each histone can be
modified by the covalent attachment of a number of different chemical groups, mainly to the tails. The tail of histone H3, for example,
can receive acetyl groups (Ac), methyl groups (M), or phosphate groups (P). The numbers denote the positions of the modified amino
acids in the histone tail, with each amino acid designated by its one-letter code. Note that some amino acids, such as the lysine (K) at
positions 9, 14, 23, and 27, can be modified by acetylation or methylation (but not by both at once). Lysines, in addition, can be modified
with either one, two, or three methyl groups; trimethylation, for example, is shown in (B). Note that histone H3 contains 135 amino
acids, most of which are in its globular portion (represented by the wedge); most modifications occur on the N-terminal tail, for which
36 amino acids are shown.
(B) Different combinations of histone tail modifications can confer a specific meaning on the stretch of chromatin on which they occur, as
indicated. Only a few of these functional outcomes are known
Chromatin-remodeling complexes
• Is another mechanism for regulation of chromosome structure

• Help locally reposition the DNA wrapped around nucleosomes
 Changes in nucleosome structure
 Allow access to DNA
• Histone-modifying enzymes work in concert with the chromatin-remodeling complexes to condense and relax
stretches of chromatin, allowing local chromatin structure to change rapidly according to the needs of the cell
Schematic representation of main epigenetic
mechanisms. (A) Histone Modifications: These
modifications involve: histone
acetyltransferases (HATs), histone deacetylases
(HDACs), or histone methyltransferases [e.g.,
tri-methylation the 4th lysine residue of the
histone protein (H3K4Me3) involving Polycomb
(PRC1 and PRC2), Trithorax (TRx), and
COMPASS (complex proteins associated with
SET1)]. (B) DNA Methylation: transfer of a
methyl group (CH3) onto the C5 position of the
cytosine to form 5-methylcytosine. In (A, B):
H2B, H3, H4, H2A = Core histone. (C)
microRNAs (regulatory RNAs) can affect
alternative splicing and protein expression.
Illustration of biosynthesis: transcription of
miRNA gene by RNA polymerase II or III to form
primary miRNA (Pri-miRNA), which are then
cleaved and some may be circulating
Frontiers in Psychiatry |
www.frontiersin.org (June 2020 |
Volume 11 | Article 579)
• Interphase chromosomes occupy their
An Interphase Nucleus
own distinct territories within the
nucleus.
• Most obvious ex: nucleous
• Note: pairs of homologous
chromosomes, such as the two copies of
Chr 9 indicated, are not generally located
in the same position
• The structure of chromatin varies along a
single interphase chromosome
X inactivation: an obvious example of
heterochromatin
Question 1: Women with Turner syndrome have just

one X chromosome but women usually only have
one working X because of X-inactivation. Why do
women with one X chromosome have any
symptoms?
Question 2: Mutations in a particular gene on the X

chromosome result in color blindness in men. By
contrast, most women carrying the mutation have
proper color vision but see colored objects with reduced
resolution, as though functional cone cells (the
photoreceptor cells responsible for color vision) are
spaced farther apart than normal in the retina. Can you
give a plausible explanation for this observation? If a
woman is colorblind, what could you say about her
father? About her mother? Explain your answers.
A Mitotic Nucleus
• DNA highly condensed
• chromosome structure is visible.
• Human karyotype: an
ordered display of the full set
of 46 human chromosomes
• Cytogeneticists analyze
karyotypes to detect
chromosomal abnormalities
that are associated with
some inherited defects and
with certain types of cancer
4/ DNA REPLICATION
4.1/ Theories of DNA replication and experiments by Meselson and Stahl
Video 2: MB-2
Density gradient
centrifugation
Experiments by
Meselson and Stahl,
1958
4.2/ Important rules in DNA replication
Semi-conservative
Complementary
Differences:
• Large gemome vs small
genome  multiple ORI vs
single ORI
• Circular DNA vs. Linear DNA
 Shorten of DNA each cycle
of replication (The end-
replication problem)
Similarities:
• Semi-conservative: one old strand + 1 new strand in daughter DNA (as well as daughter cell)
• Bi-directional replication: Forks advances in both directions
Question: Explain why some eukaryotic
cells such as cancer cells, germ cells can
have unlimited replication cycles ?
Base are added using TERC as
• By using TERC, TERT can add a six-nucleotide
template repeating sequence, 5'-TTAGGG (in vertebrates,
the sequence differs in other organisms) to the
3' strand of chromosomes. These TTAGGG
repeats (with their various protein binding
partners) are called telomeres. The template
region of TERC is 3'-CAAUCCCAAUC-5'.
• Telomerase can bind the first few nucleotides of
the template to the last telomere sequence on
the chromosome, add a new telomere repeat
(5'-GGTTAG-3') sequence, let go, realign the new
3'-end of telomere to the template, and repeat
the process. Telomerase reverses
telomere shortening.
Similar:
- Read template 3’ 5’
- Synthesize new strand 5’  3’
(add from 3’OH)
- Complementary
- Antiparallel
Different:
- Subtrate: dNTP vs NTP
Proofreading - Primer required vs not required
3’  5’exonuclease activity - Proofreading vs not proof
reading
Correct Incorrect
Comparison of DNA and RNA Polymerases
4.3/ Steps in DNA Replication in prokaryote
DnaA recognizes and
1 binds to ORI
Helicase (DnaB) breaks hydrogen

bond, Single-stranded binding
2
proteins (SSBP) stabilize single-
3 strand form
Enzyme primase synthesize

4 primers (DNA polymerase can
only build onto 3 end of an
existing DNA strand)
5 DNA polymerase III begins synthesizing DNA
5 Lagging
3 5 3 strand
5
3
3 5
growing 3 primase
replication fork DNA polymerase III
5
RNA 5
Leading
3 strand
DNA polymerase III can only build from 5’ to
3’ direction
6 DNA polymerase I both removes the primer
(5' exonuclease) and synthesizes new DNA;
7 “proofreading” process
DNA polymerase I still can only build
onto 3 end of an existing DNA strand
8 DNA ligase seals the "nicks"

between Okazaki fragments,
9 DNA gyrase (DNA topoisomerase II)

provides a "swivel" in front of each
replication fork.
https://www.khanacademy.org/science/biology/dna-as-the-gen
etic-material/dna-replication/a/telomeres-telomerase?modal=
1
A real eukaryotic chromosome

would have multiple origins of
replication and multiple
replication bubbles, but the
end-replication problem would
be the same as shown above.
Image modified from "
Telomere shortening," by Zlir'a,
public domain.
(A) For simplicity, the diagram shows the proteins
working independently
(B) Current view of how the replication proteins are

arranged at the replication fork when the fork is
moving. In the cell, proteins are held together in a large
replication machine
- DNA synthesis is carried

out by a group of proteins that act together
as a replication machine
4.4/ DNA Replication in eukaryote
The mechanism of replication in eukaryotes is
believed to be very similar to this. However,
the details have not yet been completely
worked out.
Summary of Steps and Proteins Involved in DNA Replication
Quinolones: Etoposide,
Ciprofloxacin, Teniposide
Moxifloxacin,
Levofloxacin
Video 3: MB-3
* Single-strand 5/ DNA REPAIR Clinical correlates:
Page 24, 27
damage
Nucleotide-excision
repair (NER)
Mismatch repair
Base-excision
repair (BER)
Important Genes Associated with
Maintaining Fidelity of Replicating DNA
Errors accumulated
during G1 need to be
removed before the cells
enters the S-phase
• Pharmacy students and Odonto stomatology: self-reading
* Double-strand
damage
Cells can repair double-

strand breaks in one of
two ways.
Important note: The average number of SNP mutations per
diploid genome per generation is estimated to be 70
6. HUMAN GENOME AND PHARMACOGENETICS/GENOMICS
How to read a DNA sequence?

• Approximately 50% of
the human genome is
made up of high-copy
repetitive sequences
Source: Study of Genetic Variations of 15 Autosomal short Tandem Repeats (STRs) and Amelogenin Loci to Establish
Database for Iraqi Population
DO - 10.13140/RG.2.2.15139.35360
DNA Polymorphisms
• Humans share around 99.5 percent of their genomes.
• The 0.5 percent that does differ between each of us affects our
susceptibility to disease and response to drugs.
• Differences/variations in human genomes are named polymorphisms
• Two types of variation are common in the human genome:
Single nucleotide polymorphisms (SNPs): changes in single nucleotide
bases? (A, C, G and T): account for 90% of all human genetic variations.
99% of them have no biological effect.
Structural variation: changes affecting chunks of DNA which can
consequently alter the structure of the entire chromosome.
Precision medicine and pharmacogenetics
• Precision medicine is a healthcare approach that utilises molecular
information (genomic, transcriptomic, proteomic, metabolomic, etc),
phenotypic and health data from patients to generate care insights to
prevent or treat human disease resulting in improved health outcomes”.
• In cancer, precision medicine involves testing DNA from patients’ tumors
to identify the mutations or other genetic changes that drive their
cancer. Physicians then may be able to select a treatment for a particular
patient’s cancer that best matches, or targets, the culprit mutations in
the tumor DNA.
• Many cancers (such as breast cancer, lung cancer are already benefiting
from precision medicine treatments
Source: https://databridgemarketresearch.video.blog/2019/06/06/global-precision-medicine-market-industry-
trends-and-forecast-to-2024/
• Pharmacogenomics is a core part of precision medicine. Pharmacogenomics is the
study of how genetic makeup of an individual affects his/her response to drugs by
correlating genetic variants with a drug's efficacy or toxicity.
Source: Psychiatry Research Volume 292, October 2020, 113336

EXTENSION:
SARS-CoV-2 GENOME, MUTATION and

VARIANTS
Cite: Nature Communications volume 12, Article number: 2642 , May,https://www.sciencedirect.com/science/article/pii/S221112472100961X
2021
• 29,903-nucleotide positive-strand RNA genome (largest RNA viral genome)

• Encodes ~30 known and candidate mature proteins with several open-reading frames (ORFs) whose function or even
protein-coding status is unknown
• Contain 6 ORFs that are common to all coronaviruses include:
 Two large ORFs, ORF1a and ORF1b , encoding 16 NSP (Nsps within ORF1a are largely responsible for control of genome
expression and those within ORF1b for replication, Some nsps function in host-cell suppression, immune suppression,
and diverse viral functions)
 Four ORFs encoding 4 structural proteins: S, E, M, N previously identified in other viruses of the species, namely, from 5′
to 3′, ORFs 3a, 6, 7a, 7b, and 8
• Contain other unnamed ORFs: ORFs 3a, 6, 7a, 7b, 8, 9b, pc, 10, many of these encoding accessory proteins
https://post.parliament.uk/sars-cov-2-virus-variant
a-year-into-the-covid-19-pandemic/
CITE: WHO, MAY, 2021

1. Giải thích học thuyết trung tâm của sinh học phân tử, nêu những trường hợp xảy ra quá trình phiên mã ngược
2. So sánh giữa biểu hiện gen và sao chép DNA; và so sánh giữa DNA polymerase với RNA polymerase
3. Trình bày được một số tác nhân hóa trị liệu có cơ chế tác động lên các pha của chu kỳ tế bào
4. Nêu được các thành phần cấu trúc cơ bản của 1 nucleoside và 1 nucleotide, phân biệt được từng loại bazo nito và
từng nhóm bazo nito, cách đọc danh pháp nucleoside và nucleotide
5. Trình bày được các đặc điểm cấu trúc quan trọng của chuỗi xoắn kép Waston-Crick và so sánh sự tổ chức (đóng
gói) của DNA ở bộ gen tế bào nhân thực và nhân sơ
6. So sánh được heterochromatin (vùng dị nhiễm sắc) với euchromatin (vùng đồng nhiễm sắc) và giải thích được vai
trò của DNA methylation, và các thay đổi trên histon (acetylation và phosphorylation) đối với biểu hiện gen
7. So sánh ngắn dọn sao chép DNA giữa nhân sơ và nhân thực; giải thích tại sao các tế bào nhân thực như tế bào ung
thư, tế bào mầm sinh sản, tế bào gốc có số lần phân bào không giới hạn; cấu trúc và cơ chế hoạt động của enzyme
telomerase
8. Trình bày các bước cơ bản trong sao chép DNA ở prokaryote và khác biệt cơ bản trong sao chép DNA ở eukaryote
so với ở prokaryote
9. Trình bày ý nghĩa của sửa sai DNA, các cơ chế chính trong sửa sai mạch đơn và các ví dụ bệnh lý liên quan
10. Trình bày được các điểm quan trọng trong bộ gen người, các khái niệm polymorphism, precision medicine,
pharmacogenetics, ví dụ cho precision medicine
Self-studying
Chapter 9
HOW GENES AND GENOME EVOLVE

1. GENERATING GENETIC VARIATION
2. RECONSTRUCTING LIFE’S FAMILY TREE
3. MOBILE GENETIC ELEMENTS AND VIRUSES
4. EXAMINING THE HUMAN GENOME
Câu hỏi: So sánh khác biệt cơ bản giữa transposon và virus và

trình bày ngắn gọn các thành phần DNA trong bộ gen người
Molecular Biology: Unit 2
TRANSCRIPTION AND
TRANSLATION

Email: hangdo009@gmail.com
REFERENCES:
• Biochemistry and Medical Genetics – Kaplan USMLE Lecture
Notes – 2021, Section I : chapter 3, chapter 4
• Essential Cell Biology (5th Edition, 2019) written by Albert,
Bray, Hopkin, et al, Chapter 7
MAIN CONTENTS
1. TRANSCRIPTION
2. THE GENETIC CODE
3. MUTATIONS
4. TRANSLATION
5. PROTEIN FOLDING, TRAFFICKING, AND MODIFICATION
1/ TRANSCRIPTION 1.1/ Overview of Transcription
Facts about Transcription:
- Not all DNA is transcribed (In human: ~ 3-4% transcribed, in which ~ 1.5% translated) and transcription (gene
expression) differs among tissues
- RNA polymerase initially finds and binds to the promoter, not the coding region
- “Gene” = dsDNA but only one strand is used as template for transcription
 Template strand is used in transcription and is complementary to the mRNA product
 Coding strand is NOT used but is identical to mRNA (T/U) and has TATA sequence
Coding
strand
Is the promoter transcribed?

No (RNA polymerase starts at +1)
Coding
Template
Template Coding
Transcription of Several Genes on a Chromosome
• mRNA
Types of RNA: • rRNA (most abundant)
• tRNA
• Others (snRNA, miRNA, ribozymes…)
Comparison of RNA Polymerases
(= Core enzyme)
Amanita genus of mushrooms Tuberculosis, Meningitis Orange-color of Urine, stool, saliva…

Transcription of DNA
Flow of Genetic Information from DNA to Protein
1.2/ PRODUCTION OF PROKARYOTIC MESSENGER RNA
A prokaryote
transcription unit:
- Promoter
- Coding region
- Terminator
Polycistronic Gene Region Codes for Several Different
Proteins
Signals in the nucleotide sequence of a gene
tell bacterial RNA polymerase where to start
and stop transcription.
Bacterial RNA polymerase (light blue) contains
a subunit called sigma factor (yellow) that
recognizes the promoter of a gene (green).
Once transcription has begun, sigma factor is
released, and the polymerase moves forward
and continues synthesizing the RNA.
Elongation continues until the polymerase
encounters a sequence in the gene called the
terminator (red). After transcribing this
sequence into RNA (dark blue), the enzyme
halts and releases both the DNA template and
the newly made RNA transcript. The
polymerase then reassociates with a free
sigma factor and searches for another
promoter to begin the process again.
Bacterial promoters and terminators have specific nucleotide sequences that are recognized by RNA polymerase.
(A) The green-shaded regions represent the nucleotide sequences that specify a promoter. The numbers above the
DNA indicate the positions of nucleotides counting from the first nucleotide transcribed, which is designated +1. The
polarity of the promoter orients the polymerase and determines which DNA strand is transcribed. All bacterial
promoters contain DNA sequences at –10 and –35 that closely resemble those shown here.
(B) The red-shaded regions represent sequences in the gene that signal the RNA polymerase to terminate transcription.
Note that the regions transcribed into RNA contain the terminator but not the promoter nucleotide sequences.
The transcription in prokaryote occurs in 3 steps:
Step 1: Holoenzyme
Transcription
initiation
Step 2:
Transcription
Elongation
Step 3: Transcription Termination
Two mechanisms of
transcription
termination: Rho-
dependent
mechanism and
Rho-independent
mechanism
Note:
• After transcription has been completed, mRNAs are degraded by RNAses in the cytosol and their
nucleotide building blocks are reused for transcription
• Many eukaryotic mRNAs have a longer lifetime than bacterial mRNAs
• The different lifetimes of eukaryotic mRNAs are controlled in part by nucleotide sequences in the mRNA itself
1.3/ PRODUCTION OF EUKARYOTIC MESSENGER RNA
A Eukaryotic
Transcription Unit:
- Promoter
- Coding region
- Terminator
Processing of
Eukaryotic Pre-
Messenger RNA
Co-transcriptional
Post-transcriptional
Post-transcriptional
ALTERNATIVE SPLICING OF EUKARYOTIC PRIMARY PRE-
mRNA TRANSCRIPTS
Hydrophobic vs. hydrophilic

A specialized set of RNA-binding proteins signals that a completed mRNA is ready for export to the cytosol.
As indicated on the left, the 5’ cap and poly-A tail of a mature mRNA molecule are “marked” by proteins that
recognize these modifications. Successful splices are marked by exon junction complexes Once an mRNA is
deemed “export ready,” a nuclear transport receptor associates with the mRNA and guides it through the
nuclear pore. In the cytosol, the mRNA can shed some of these proteins and bind new ones, which, along
with poly-A-binding protein, act as initiation factors for protein synthesis
Transcription initiation in eukaryote is more complex
• RNA polymerase II cannot recognize a

promoter sequence. Instead, other proteins
known as basal transcription factors bind to
the promoter and guide RNA polymerase II
to the beginning of the gene to be
transcribed
• TATA box, binds a protein called the
transcription factor IID (TFIID), one of
whose subunits is called the TATA-binding
protein, or TBP.
• Other transcription factors include TFIIA,
TFIIB, TFIIE, TFIIF, and TFIIH.
Summary of Important Points About Transcription and RNA
Processing
Summary of Important Points About Transcription and RNA
Processing (Ct.)
2/ THE GENTIC CODE
What UUA code for ?

(Leu)
What CAG code for?

(Gln)
Main features of • Universal: Except in mitochondria
• Degenerate: UUU & UUC = Phe
the genetic code • Unambiguous: UUU = Phe always
• Continuous = Not overlap, Not intermittent
64 Possible Codons:
• 61 encode AA (includes 1 start codon: AUG)
• 3 stop codon
 UAG = You are gone
 UGA = You go away
 UAA = You are away
??? Reading frame vs. Open reading frame (ORF) vs. Coding sequence (CDS)
3/ MUTATIONS IN CDS
Effects of Some
Common Types
of Mutations on
Protein
Structure
• Hungtington’s Disease CAG

4/ TRANSLATION
4.1/ Factors involving in translation
• The synthesis of proteins is quite complex, requiring three types
of RNA.
• Messenger RNA (mRNA): contains the code and is the template for
protein synthesis.
• Transfer RNAs (tRNAs) are adapter molecules that carry amino acids
to the mRNA.
• Ribosomal RNAs (rRNAs) form part of the ribosome that brings
together all the components necessary for protein synthesis.
• Several enzymes also help in the construction of new protein
molecules
TRANSFER RNA (tRNA) CARRIES ACTIVATED AMINO ACIDS FOR
TRANSLATION
The genetic code is translated by aminoacyl-tRNA synthetases and tRNAs. Each synthetase
couples a particular amino acid to its corresponding tRNAs, a process called charging. The
anticodon on the charged tRNA molecule then forms base pairs with the appropriate codon on
the mRNA. An error in either the charging step or the binding of the charged tRNA to its codon
will cause the wrong amino acid to be incorporated into a polypeptide chain. In the sequence of
events shown, the amino acid tryptophan (Trp) is specified by the codon UGG on the mRNA.
Wobble
hypothesis
the 3rd base in an

mRNA codon can
undergo non-
Watson-Crick base
pairing with the 1st
base of a tRNA AUC/AUU/AUA
anticodon
Base Pairing of an Aminoacyl-tRNA with Codon in mRNA

RIBOSOMAL RNA (rRNA) IS USED TO CONSTRUCT
RIBOSOMES
Shiga toxin,
Verotoxin:
remove an
specific Adenin
of 28S
Eukaryote ribosome: 4 types of rRNA + 82

different proteins
The ribosome has three active sites: the A site, the P site, and the E site.
- The A site is the point of entry for the aminoacyl tRNA (except for the first aminoacyl tRNA,
which enters at the P site).
- The P site is where the peptidyl tRNA is formed in the ribosom
- The E site which is the exit site of the now uncharged tRNA after it gives its amino acid to the
growing peptide chain
4.2/ Major steps in translation
1. Free amino acids are attached to tRNA molecules.
2. A ribosome assembles on the mRNA strand to initiate synthesis.
3. The ribosome travels along the mRNA. At each codon on the RNA
a tRNA binds, bringing the amino acid defined by that codon to
be added to the growing polypeptide chain.
4. The ribosome encounters a stop codon and protein synthesis is
terminated
Overview of protein synthesis (translation)
Peptide Bond Formation
Steps in
Translation
1. Initiation
2. Elongation
Steps in Translation
(Ct.)
3. Termination
POLYSOMES
Many ribosomes reading one mRNA form a polyribosome

4.3/ Some bacteria and virus cause disease because they
inhibit eukaryotic protein synthesis.
• Corynebacterium diptheriae (which causes diptheria) produces an

enzyme (diphtheria toxin) that inactivates eukaryotic elongation factor
2 (the equivalent of the bacterial elongation factor G)  Protein
synthesis therefore stops in the affected human cells. The advantage
of this to the bacterium is that all the amino acids that the host was
using to make protein are now available for its own use.
• Similarly, Hepatitis C mRNAs do not have a 7-methyl guanosine cap
at their 5’ ends. Instead they have internal ribosome entry sites
(IRES), which are specific sequences to which the ribosomes bind
tightly. The clamping of the ribosome to the IRES forces initiation of
viral protein synthesis at the expense of host cell protein synthesis.
4.4/ Antibiotics and Protein Synthesis
• Many antibiotics only inhibit protein synthesis in bacteria
and not in eukaryotes
• Examples are chloramphenicol, which blocks the peptidyl
transferase reaction, and tetracycline, which inhibits the
binding of an aminoacyl tRNA to the A site of the
ribosome. Both of these antibiotics therefore block chain
elongation.
• Streptomycin, on the other hand inhibits the formation of
the 70S initiation complex because it prevents tRNA fmet
from binding to the P site of the ribosome
The antibiotic puromycin inhibits protein
synthesis
Puromycin causes the premature release of

polypeptide chains from the ribosome and
acts on both bacterial and eukaryotic cells.
Puromycin can occupy the A site of the

ribosome because its structure resembles
the 3’end of an aminoacyl-tRNA. However,
puromycin does not bind to the mRNA.
Once translocation has occurred, the

growing polypeptide has no strong
attachment to the mRNA and is therefore
released from the ribosome.
5/ PROTEIN FOLDING, TRAFFICKING AND
MODIFICATION
• Many proteins require posttranslational modifications to become fully functional.
• To be useful to the cell, a completed polypeptide must fold correctly into its three-
dimensional conformation and then bind to required cofactors and protein
partners—all via noncovalent bonding.
• Many proteins also require one or more covalent modifications to become active—
or to be recruited to specific membranes or organelles. Although phosphorylation
and glycosylation are the most common, more than 100 types of covalent
modifications of proteins are known.
• Generally, four levels of protein shape are distinguished:
Primary
Secondary
Tertiary
Quaternary
• Some proteins can fold spontaneously, as
5.1/ Molecular they emerge from the ribosome. Most,
chaperones and however, require the assistance of
chaperone proteins
proteosome • Molecular chaperones are a class of
proteins that interact with diverse protein
substrates to assist in their folding, with a
critical role during cell stress to prevent the
appearance of folding intermediates that
lead to misfolded or otherwise damaged
molecules
• Molecular chaperones function in many cell
compartments, including the endoplasmic
reticulum, where extensive protein
synthesis occurs.
• Failure to fold correctly usually results in
eventual destruction of the protein.
Ubiquitin:
Proteasomes and Ubiquitin • small protein ~76 amino acid
• found in all eukaryotes but not
in prokaryotes
Misfolded proteins marked by a polyubiquitin chain are degraded by the proteasome.
Clinical Correlate: Cystic Fibrosis

5.2/ Protein sorting/trafficking
Membrane-enclosed organelles import proteins by one of three
mechanisms. All of these processes require energy. The protein remains
folded during transport in mechanisms 1 and 3 but usually has to be
unfolded during mechanism 2
Important note:
 Proteins are translated on ribosomes associated with
the rough endoplasmic reticulum (RER) (and then
transported by vesicles) include:
• Secreted proteins
• Proteins inserted into the cell membrane
• Lysosomal enzymes
 Proteins translated on free cytoplasmic ribosomes

include:
• Cytoplasmic proteins
• Mitochondrial proteins encoded by nuclear genes (transported
across organelle membrane)
• Peroxisome proteins (transported across organelle membrane)
• Nuclear proteins (transport through nuclear pores)
Synthesis and transport of Secretory, Membrane, and
Lysosomal Proteins
Proteins are dispatched to
different locations in the
cell according to specific
address labels (sorting
signal) contained in their
amino acid sequence.
Important examples are:
• The N-terminal
hydrophobic signal
sequence used to target
the translating protein on
the RER
• Phosphorylation of
mannose residues
important for directing an
enzyme to a lysosome
Accumulation or ineffective targeting of misfolded
proteins
• In certain genetic diseases, the mutation may cause all copies of the
protein to fold incorrectly.
• The result is loss of protein function and, in some cases, accumulation
of the misfolded protein in the endoplasmic reticulum.
Clinical correlate: α1-Antitrypsin Deficiency

Lysosomal Enzymes and Phosphorylation of
Mannose
• Specific mannose residues in lysosomal enzyme are
phosphorylated by n-acetylglucosamine- 1
phosphotransferase  This phosphorylation is the
critical event that removes them from the secretion
pathway and directs them to lysosomes.
Cinical correlate: I-cell disease

5.3/ CO- AND POSTTRANSLATIONAL COVALENT
MODIFICATIONS
In addition to disulfide bond formation while proteins are folding, other
covalent modifications include:
• Glycosylation: addition of oligosaccharide as proteins pass through the ER and
Golgi apparatus
• Proteolysis: cleavage of peptide bonds to remodel proteins and activate them
(proinsulin, trypsinogen, prothrombin)
• Phosphorylation: addition of phosphate by protein kinases
• y-Carboxylation: produces Ca2+ binding sites
• Prenylation: addition of farnesyl or geranylgeranyl lipid groups to certain
membrane-associated proteins
SYNTHESIS AND POSTTRANSLATIONAL MODIFICATIONS OF COLLAGEN
Synthesis of Collagen
Types of collagen
Disorders of Collagen Biosynthesis
SUMMARY Important Points About the Genetic Code, Mutations, and
Translation
SUMMARY Important Points About the Genetic Code, Mutations, and
Translation (Cont.)
EXTENSION 1:
MOLECULAR
MECHANISMS OF
COVID19-VACCINES
Source: Not available in Canada: A look at COVID
-19 vaccine tech from China, India and Cuba | CBC
Source: Not available in Canada: A look at COVID
-19 vaccine tech from China, India and Cuba | CBC News
Viral vector vaccine
•Viral vector vaccines use a

modified version of a different
virus (the vector) to deliver
important instructions to our
cells.
•mRNA vaccines are a new type of vaccine to protect against infectious diseases.
•mRNA vaccines teach our cells how to make a protein—or even just a piece of a protein—
mRNA Vaccine that triggers an immune response inside our bodies.
•The benefit of mRNA vaccines, like all vaccines, is those vaccinated gain protection
without ever having to risk the serious consequences of getting sick with COVID-19.
•COVID-19 vaccines are not interchangeable. If you received a Pfizer-BioNTech or
Moderna COVID-19 vaccine, you should get the same product for your second shot
Source:
Understanding
mRNA COVID-19
Vaccines | CDC
Nature
Illustration of the mechanism of action of vaccines Reviews
Immunology
volume 21, p
ages195–197
(2021)
1. Nêu các lưu ý quan trọng về phiên mã và các khác biệt chính giữa mRNA của prokaryote và eukaryote
2. Trình bày được cấu trúc cơ bản của 1 đơn vị phiên mã ở prokaryote và ở eukaryote
3. Trình bày quá trình xử lý tiền mRNA ở eukaryote và ý nghĩa của các bước đó
4. Tóm tắt được diễn biến 3 bước trong phiên mã ở prokaryote (khởi đầu, kéo dài, kết thúc). Khác biệt lớn nhất
trong quá trình phiên mã ở eukaryote so với prokaryote nằm ở giai đoạn nào, giải thích.
5. Nêu các đặc điểm quan trọng của mã di truyền và liệt kê các loại đột biến điểm xảy ra trên CDS cũng như
ảnh hưởng của chúng lên protein
6. Nêu vai trò của từng loại RNA trong dịch mã và tóm tắt các bước của quá trình dịch mã, các khác biệt chính
trong dịch mã ở prokaryote so với eukaryote
7. Nêu chức năng của chaperon và proteosome đối với protein. Mô tả tóm tắt bệnh xơ nang và cơ chế phân tử
của bệnh
8. Vai trò của các tín hiệu “ N-terminal hydrophobic signal sequence” và “Phosphorylation đường mannose”
trên protein là gì? Mô tả tóm tắt bệnh I-cell và cơ chế phân tử của bệnh
9. Trình bày tóm tắt một số ví dụ trong đó dịch mã ở tế bào chủ bị ức chế bởi một số vi sinh vật (như
Corynebacterium diptheriae, HCV) hay một số kháng sinh (chloramphenicol, streptomycin, puromycin) ức
chế dịch mã ở vi khuẩn
10. Nêu tóm tắt cơ chế phân tử - tế bào của các nhóm vaccine Covid-19
Chapter 2
COMPONENTS OF CELLS
1. CHEMICAL BONDS
2. SMALL MOLECULES IN CELLS
3. MACROMOLECULES IN CELLS
Câu hỏi: Tế bào có tới 70% là nước, 30% còn lại bao gồm các thành phần gì?
Trình bày ngắn gọn cấu tạo và chức năng của 4 nhóm đại phân tử trong tế bào
Chapter 9
HOW GENES AND GENOME EVOLVE

1. GENERATING GENETIC VARIATION
2. RECONSTRUCTING LIFE’S FAMILY TREE
3. MOBILE GENETIC ELEMENTS AND VIRUSES
4. EXAMINING THE HUMAN GENOME
Câu hỏi: So sánh khác biệt cơ bản giữa transposon và virus và

trình bày ngắn gọn các thành phần DNA trong bộ gen người
Chapter 15
INTRACELLULAR COMPARTMENTS AND PROTEIN

TRANSPORT
1. MEMBRANE-ENCLOSED ORGANELLES
2. PROTEIN SORTING
3. VESICULAR TRANSPORT
4. SECRETORY PATHWAYS
5. ENDOCYTIC PATHWAYS
Câu hỏi: Membrane trafficking (vesicle transport) khác biệt cơ bản như thế
nào so với vận chuyển đi qua màng (transport across membrane). Nêu 2
con đường của membrane trafficking và ví dụ cho mỗi con đường
Chapter 20
CELLULAR COMMUNITIES: TISSUES, STEM CELLS, AND

CANCER
1. EXTRACELLULAR MATRIX AND CONNECTIVE TISSUES
2. EPITHELIA SHEETS AND CELL JUNCTION
3. STEM CELLS AND TISSUE RENEWAL
4. CANCER
Câu hỏi: Nêu 2 tính chất chính của tế bào ung thư. Tại sao đối với đa số
các loại ung thư, tỉ lệ mắc bệnh tăng theo độ tuổi

DR Hằng Và Dr Nam Tổng Hợp Bài Giảng

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DR Hằng Và Dr Nam Tổng Hợp Bài Giảng

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ĐẠI HỌC QUỐC GIA TP.

HCM CỘNG HÒA XÃ HỘI CHỦ NGHĨA VIỆT NAM

KHOA Y Độc lập – Tự do – Hạnh phúc

ĐỀ CƯƠNG CHI TIẾT MÔN HỌC

Thuộc khối kiến thức: Đại cương

2. Số tín chỉ: 3 Lý thuyết: 2 Thực hành: 1

3. Trình độ: Sinh viên năm 1

4. Phân bổ thời gian: Học kỳ II, năm 1

5. Điều kiện tiên quyết: Không

Mục tiêu đào tạo Chuẩn đầu ra

8. Mô tả vắn tắt nội dung môn học

9. Tài liệu tham khảo

10. Nhiệm vụ của sinh viên

- Sinh viên dự lớp đúng giờ và đầy đủ.

 Vắng 50% số lần kiểm tra của môn học.

11. Phương thức đánh giá và cho điểm

- Điểm báo cáo seminar nhóm

Điểm cuối kỳ - Điểm thi cuối kỳ (Trắc

- Các điểm thành phần được làm tròn đến 0,1

Xuất sắc Từ 9,0 đến 10,0 Từ 90 đến 100 4,0 A+

Giỏi Từ 8,0 đến cận 9,0 Từ 80 đến cận 90 3,5 A

Khá Từ 7,0 đến cận 8,0 Từ 70 đến cận 80 3,0 B+

Trung bình Từ 5,0 đến cận 6,0 Từ 50 đến cận 60 2,0 C

Yếu Từ 4,0 đến cận 5,0 Từ 40 đến cận 50 1,5 D+

Từ 3,0 đến cận 4,0 Từ 30 đến cận 40 1,0 D

11.3. Các lưu ý:

12. Chính trực trong học thuật

13. Nội dung học tập:

Hình thức dạy

I/ Section I: Cell Biology

2 của tế bào (Chemical 8 Biology (5th Edition), Garland Science,

components of cells) 2019

- Giảng viên: TS. Nguyễn Minh Nam

Quần thể tế bào: mô, tế - TLTK: Albert el al., Essential Cell

II/ Section II: Molecular Biology and Medical Genetics

- Giảng viên: TS. Đỗ Thị Thu Hằng

- Giảng viên: TS. Đỗ Thị Thu Hằng

- Giảng viên: TS. Bùi Chí Bảo

- Giảng viên: TS. Bùi Chí Bảo

Sự tiến hóa của gen và bộ - TLTK: Albert el al., Essential Cell

- Giảng viên: ThS.BS. Trần Thị Kim

- Giảng viên: ThS.BS. Trần Thị Kim

13.2. Thực hành

Hình thức dạy

-Giảng viên: ThS. Huỳnh Thị Diệu

(Determine the concentration

-Giảng viên: TS Đỗ Thị Thu Hằng;

-Giáo trình thực tập Sinh học Đại

TP. HCM, ngày tháng năm 2022

GS.TS.BS. ĐẶNG VẠN PHƯỚC

• Why do you need to study this subject?

Cell Biology: Unit 1

THE OVERVIEW OF CELLS:

Lecturer: Đỗ Thị Thu Hằng

• Essential Cell Biology (5th Edition, 2019)

1. OVERVIEW OF CELL AND CELL THEORY

Theodor Schwann, 1839:

Rudolf Virchow, 1855:

The modern version of the cell theory:

there may be up to 100 million distinct species of living things on our

• One of largest groups on

Why don’t archaea cause disease? | M

• Control center of cell