chap 1.1 to 1.

科學的範疇
require
自然科學 數學
1.物理科學
1.物理科學 2.生物
2.生物科學
生物科學
(研究物質及能量)
研究物質及能量)

動動動動物學

植植植植物學
跨領域
地質學

物理學
天文學

跨領域 化學
生物化學
化學物理 醫學化學
物理化學
生物物理化學

生態學
生理學
微生物學
遺傳學
原子分子
分析化學

物理化學

有機化學

無機化學

chap 1.1 to 1.2 1

化學與物理
量子力學(quantum mechanics)
本世紀初，
本世紀初，量子力學肇始並宣稱已解決
所有的化學問題及一半的物理問題

：ΗΨ=ΕΨ
Schrodinger Equation：ΗΨ ΕΨ
Η：Hamiltonian operator
Ψ：wavefunction
Ε：energy
所有的分子性質、
所有的分子性質、化學反應皆可由此
推測
Schrodinger Equation推測
然而現今只能成功地推測小分子！！
然而現今只能成功地推測小分子！！
chap 1.1 to 1.2 2

1
 chap 1.1 to 1.2

化學與應用化學
•材料科學
材料科學：
材料科學：金屬材料
高分子材料
電子工程：
電子工程：電子材料
化學工程：
化學工程：將化學實驗室的製程放大
食品：
食品：食品添加物
生化及藥化產業：
生化及藥化產業：製藥、
製藥、生物科技

chap 1.1 to 1.2 3

Chapter 1
Foundations of Biochemistry
What is Chemistry？ ？
：
This science that tries to understand：
(A)The properties of substances
(B)The changes that substances undergo
The realm of substances： ：
(A)Natural substances： ：
e.g.water, air, element, salt...
(B)New compounds created by chemists
e.g.polymer ,nylon...
：
(C)Chemicals found in living creatures：
e.g.DNAs, proterins, carbohydrates...
：
Biochemistry tries to understand：
(A)The properties of biomolecules
(B)The changes that biomolecules undergo 4
chap 1.1 to 1.2

2
 chap 1.1 to 1.2

The differences between livings and inanimate objects

1. A high degree of chemicail complexity &
microscopic organization
2. Living organisms extract, transform,and use
“energy” from their environments, usually in the
form of chemical nutrients or sunlight.
3. Defined functions for each of an organism’s
components and regulated interactions among
them
4. Mechanisms for sensing and responding to
alterations in their surrounding
5. Living organisms are capable of “self-assemby”
and self-replication
6. A capacity to change over time by gradual
chap 1.1 to 1.2 5
evolution

Biochemistry explains diverse forms of life in

：
unifying chemical terms：
異(巨觀)
巨觀) 同(微觀)
微觀)
Living organisms are Living organisms are
：
enormously diverse： remarkably alike at the
animals、、plants cellular and chemical levels

：
Biochemistry describes：
1.The structures, mechanisms, and chemical processes
shared by all organisms in “molecular terms”
2.Provides organization principles that underlie life

chap 1.1 to 1.2 The molecular logic of life 6

3
 chap 1.1 to 1.2

The molecular logic of life

• Consider the properties of living organisms

• Describe a set of principles that characterize
all living organism

Diverse living organisms

share common chemical
chap 1.1 to 1.2 features 7

1.1 Cellular Foundations

Cells are the structural and functional units of all
living organisms

chap 1.1 to 1.2
Cells:
1. Plasma membrane：
defines the periphery of the
cell, separating its contents
from the surroundings.
It is composed of lipid and
protein molecules that form
a thin, tough, pliable,
hydrophobic barrier
around the cell. 8

4
 chap 1.1 to 1.2

2. Cytoplasm：
composed of cytosol and
suspended particles
Cytosols：：
enzymes, RNA molecules,
monomeric subunits (amino
acids and nucleotides),
metabolites (small organic
molecules), coenzymes.
suspended particles：：
Supramolecular structures
(like ribosomes and
proteasomes)
chap 1.1 to 1.2 9

3. Nucleus or Nucleoid：
Complete set of genes (genome)

真核生物)：
真核生物 ：
Eukaryotes (真核生物
Cells with nuclear envelopes
原核生物)：
原核生物 ：
Prokaryotes (原核生物
without nuclear envelopes

chap 1.1 to 1.2 10

5
 chap 1.1 to 1.2

Cellular Dimensions Are Limited by Oxygen

Diffusion
• Animal and plant cells are 5 to 100 µm in diameter
• many bacteria are only 1 to 2 µm long
：mycoplasmas (黴漿菌
• the smallest cells： 黴漿菌),
黴漿菌 ~300nm in
-14
diameter, and ~10 ml in volume
：defined by the rate of diffusion
•Upper limit of cell size：
of solute molecules in aquaous systems
：Set by the minimum number of
•Lower limit of cell size：
each type of biomolecule (supramolecules and organelles)
，~20nm long)
required by the cell (e.g. ribosome，

chap 1.1 to 1.2 11

There Are Three Distinct Domains of Life

真細菌)
真細菌
1. bacteria (真細菌
inhabits soils, surface waters, tissues.
e.g. E. Coli

古細菌)
古細菌
2. Archaea (古細菌
inhabits more extreme environments (salt lakes, hot
springs…) e.g. methanococcus jannasch

真核生物)
真核生物
3.Eukaryotes (真核生物

chap 1.1 to 1.2 12

6
 chap 1.1 to 1.2

There Are Three Distinct Domains of Life

包含兩個Groups
包含兩個
prokaryotes包含兩個
真細菌)
真細菌
1. bacteria(真細菌
chap 1.1 to 1.2 古細菌)
古細菌
2. archaea (古細菌 13

Organisms can be classified according to their

energy source (sunlight or oxidizable chemicals)

chap 1.1 to 1.2 14

7
 chap 1.1 to 1.2

大腸桿菌
大腸桿菌)
Escherichia coli (大腸 桿菌 is the most-studied
prokaryotic cell : 5 µm in length; 2 µm in diameter
ribosomes

membrane 伸
出：
Pili, flagella

chap 1.1 to 1.2 15

Escherichia coli is the most-studied

prokaryotic cell

：Ribosomes (15,000個
•cytoplasm： 個), enzymes (1000種種),
metabolites, and cofactors
：A single, circular molecule of DNA. 1000x
•Nucleoid：
，packed 成1 µm左右大小
length(v.s. cell)， 左右大小
•Plasmid：：Few smaller, circular molecule of DNA
Resistance to toxins and antibiotics.Amenable
to manipulation for molecular genetic study

chap 1.1 to 1.2 16

8
 chap 1.1 to 1.2

Escherichia coli is the most-studied

prokaryotic cell
Cell envelopes：
• Gram-negative bacteria (e.g. E. Coli, cyanobacteria 氰
菌, etc)
with outer membrane
peptidoglycan layer
extensive inner membrane system
• Gram-postive bacteria (e.g. Bacillus subbtilis 桿菌,
桿菌
staphylococcus aureus 葡萄球菌,
葡萄球菌 archaebacteria, etc.)
without outer membrane
pseudopeptidoglycan layer thicker
inner membrane
chap 1.1 to 1.2 17

Cell envelopes
Gram negative and positive bacteria

chap 1.1 to 1.2 18

9
 chap 1.1 to 1.2

Eukaryotic Cells Have a Variety of Membranous

Organelles, Which Can Be Isolated for Study
Typical Eukaryotic cells
5-100 μm

核仁

chap 1.1 to 1.2 19

Eukaryotic Cells Have a Variety of Membranous

Organelles, Which Can Be Isolated for Study
Plant cell

葉綠體

澱粉細粒
堆疊

類囊體

chap 1.1 to 1.2 20

10
 chap 1.1 to 1.2

Eukaryotic Cells Have a Variety of Membranous

Organelles, Which Can Be Isolated for Study

chap 1.1 to 1.2 21

補充
Eukaryotic Cells Have a Variety of Membranous
Organelles
：
Plasma membrane：
Lipid bilayer, contains transporter and receptors
1.Transporters： ：proteins that span the membrane and
carry nutrients into the cell and products out
2.Signal receptors：：bind with extra-cellular signaling
molecules (ligands): receptors recognize ligands (can be small
molecules or macromolecules).
e.g. drugs – receptor
virus/bacteria/protein – receptors
antigens - antibody
•Higher plants have cell wall(rigid, protective shell)
formed by cellulose & carbohydrate polymers outside
the plasma membrane
chap 1.1 to 1.2 22

11
 chap 1.1 to 1.2

補充
Cellular Components of Eukaryotic Cells
Endoplasmic reticulum(ER)： ：
Highly convoluted, three-dimensional network of
membrane-enclosed spaces throughout the cytoplasm
and enclosing a subcellular compartment(the lumen of
the ER)
Rough ER： ：
Granular appearance (because ribosomes attached)
Smooth ER： ：
1. the site for lipid synthesis
2. metabolism of certain drugs and toxic compound
3. In some tissues(e.g skeletal muscle), storage and
release Ca+2
chap 1.1 to 1.2 23

補充 Rough ER

smooth ER

Golgi complex
endocytosis
chap 1.1 to 1.2 exocytosis 24

12
 chap 1.1 to 1.2

補充

：
Golgi complex：
：face rough ER
• Cis side：
• Medial element
：face plasma membrane
• Trans side：
• Proteins will be modified (e.g. adding sulfate, lipid,
carbohydrate groups)

chap 1.1 to 1.2 25

補充 1.Targeted for intracellular

organelles(e.g. lysosomes)
2.Released from the cell by
exocytosis
3.Incorporate into plasma
membrane
Move to the Golgi complex
(Proteins will be modified e.g.
adding sulfate, lipid,
carbohydrate groups)

Bud

Small membrane vesicles

(Transport vesicles)
Inserted into rough ER lumen

chap 1.1 to 1.2 Proteins(during the synthesis 26

on ribosomes on rough ER)

13
 chap 1.1 to 1.2

補充

：
Ribosome：
• Synthesis of proteins
• Ribosomes attached ER synthesis protein that will
be：：
1.Released from the cell(secretory proteins)
2.Targeted for intracellular organelle(e.g. lysosome)
3.Inserted into nuclear or plasma membranes
• Cytoplasmic ribosomes synthesize proteins that will
remain and function in cytosol
chap 1.1 to 1.2 27

補充
溶酶體)：
Lysosomes(溶 ：(Only in animal cells)

• contain enzymes, capable of digesting proteins,

polysaccharides, nucleic acids, and lipids.

• act as recycling centers

分解：
分解：complex molecules carried from endocytosis
foreign cell fragment carried from phagocytosis
organelles carried from cell’s cytoplasm
分解成 a.a, monosaccharides, fatty acids.
• pH of lysosomal compartment < 5
enzymes inside are more active in acidic pH

chap 1.1 to 1.2 28

14
 chap 1.1 to 1.2

補充
過氧化氫酶
過氧化氫酶體)：
Peroxisomes(過氧化氫 ： contain catalase
2H2O2 2H2O +O2
catalase

乙醛酸循環體)：
乙醛酸循環體 ：
Glyoxysomes(乙醛酸循環體

• specialized peroxisomes in certain plant cells

• contain high conc. of enzymes of glyoxylate cycle

fats Carbohydrates
enzymes

Lysosomes, peroxisomes, and glyoxysomes

稱為 microbodies
chap 1.1 to 1.2 29

補充
Vacuoles of plant cells
• plant cells have no lysosomes.
• vacuoles carry similar “degradative” rx
•Tonoplast (the membrane surrounding the vacuole):
regulate the entry of ions, metabolites etc. for
degradation.
•Vacuole (at acidic pH) : degrade and recycle
biomolecules 的enzymes
•Vacuoles also provide physical support to the plant
因salt含量比
cell.(因 含量比cytosol高
含量比 高，產生osmotic
產生 pressure or
call turgor pressure 將cell撐起
撐起)
撐起
•Vacuoles
chap 1.1 to 1.2 含染料，
含染料，會使花果有顏色 30

15
 chap 1.1 to 1.2

補充
Nuclear Pore

chap 1.1 to 1.2 31

Nucleolus

Nucleus：：contains the genome 補充

～90 nm in diameter) associated with
•Nuclear pores(～
nuclear pore complexes specific transporters
to nucleoplasm to cytoplasm

enzymes for mRNA precursors

DNA replication and associated proteins
DNA repair
transcription
RNA processing
Chromatin(染色質 染色質)：
染色質 ：contain DNA and proteins (histones)
bound tightly together
Nucleolus： ：在nucleus中
中，含many copies of the genes
coding ribosomal RNAs (有效地 有效地transcribe
有效地 into ribosomal
chap 1.1 to 1.2 32
RNA！ ！)以備有效產生許多
以備有效產生許多ribosomes！
以備有效產生許多 ！

16
 chap 1.1 to 1.2

補充
：Nuclear division 有絲分裂
Mitosis：
：細胞分裂,
Cytokinesis：細胞分裂 胞質分裂(cell
胞質分裂 division)
Double helix

：1 ratio(重量比
Nucleosomes (DNA + histones) 1： 重量比)
重量比
帶－電 帶＋電的protein
電的
106個
Chromatin fiber

Chromatid

正在mitosis時
正在 時，mitotic chromosome
含two identical chromatid)
(含
chap 1.1 to 1.2 33

補充
體細胞)：
體細胞 ：
Somatic cells(體細胞
雙倍的)
雙倍的
have two copies of each chromosome (diploid,雙倍的

配子)
配子 (egg, sperm 生殖細胞):
Gametes(配子 生殖細胞
•have only one copy of each chromosome (haploid, 單倍的)
單倍的
有性生殖時與不同性的配子合成 zygate (合子
•有性生殖時與不同性的配子合成 合子)
合子

DNA of a single diploid human cell

104差別
拉長時：～
拉長時：～2m
：～
時：～200μ
packed時 ：～ μm

chap 1.1 to 1.2 34

17
 chap 1.1 to 1.2

補充 Mitochondria are the power plants of

Aerobic Eukaryotic cells
μm in size
•1μ
數百～
數百～1000個
•數百 個 mitochondria / eukaryotic cell
含two membrane：
•含 ：
outer membrane
inner membrane (called cristae)：：
內含物(matrix)：
內含物 ：enzymes involving in the energy-
yielding metabolism.

利用oxidation
利用 of organic nutrients
產生能量
製造ATP
製造
chap 1.1 to 1.2 35

補充
Mitochondria are the power plants of
Aerobic Eukaryotic cells

• mitochondria are produced only by division of

previously existing mitochondria.

• mitochondria contains its own DNA, RNA, and

ribosomes.

• mitochondria DNA codes for certain proteins specific

the mitochondria inner membrane.

chap 1.1 to 1.2 36

18
 chap 1.1 to 1.2

補充
葉綠體)：
葉綠體 ：power plants of plant cells
Chloroplast(葉綠體
葉綠素)
葉綠素
Pigment molecules (chlorophyll,葉綠素
在chloroplast的
的inner membranes (thylakoid類粒體
類粒體)
類粒體

adsorb solar light

make ATP

：
reduce CO2 to carbohydrates：

Mitochondria and chloroplast probably evolved from

endosymbiotic
chap 1.1 to 1.2
內共生菌).
內共生菌
bateria (內共生菌 37

The Cytoplasm is organized by the

cytoskeleton and is highly dynamic
：
Cytoskeleton：
1. actin filaments 6nm
又叫microfilament
又叫
(又叫 肌動蛋白絲)
肌動蛋白絲
2. microtubules 22nm
微管)
微管
(微管
3. intermediate filaments 6-22nm

Cytoskeletal components
constantly disassemble & reassemble
Simple protein subunits that polymerize
(location in cells, not rigidly fixed, change during
mitosis, cytokinesis….)
chap 1.1 to 1.2 38

19
 chap 1.1 to 1.2

Actin filaments Intermediate filaments

Microtubules radiating
bundled together to Extended throught the
chap 1.1 to 1.2 from the cell centers 39
form ‘stress fibers’ cytoplasm

The Cytoplasm is organized by the cytoskeleton and

(A) is highly dynamic
cytoskeletal filaments:
1. Actin filaments (in red)
2. Microtubules (in green)
nucleus (in blue)

chap 1.1 to 1.2 40

20
 chap 1.1 to 1.2

The Cytoplasm is organized by the cytoskeleton and

is highly dynamic
(B)

cytoskeletal filaments:
2. Microtubules (in green)
3. Intermediate filaments
( in red)
Chromosome (in blue)

chap 1.1 to 1.2 41

肌動蛋白)
肌動蛋白 filament (or microfilament): 6-7nm
(1) Actin(肌動蛋白
Actin sununits
actin thin filament
＋filamin ＋fordin
parallelly-linked(by fordin)
actin filament
cross-linked(by filamin)

Actin filament
+ head(binds to actin filament)
Myosin tail(binds to the membrane of a
cytoplasmic organelle)
+ ATP
move cytoplasmic organelle or vesicle along the actin
filament (called cytoplasmic streaming)
chap 1.1 to 1.2 42

21
 chap 1.1 to 1.2

*muscle contraction 亦相似

Actin filament
+
Myosin
+
ATP

muscle contraction
(See figure 5-31)
(2)microtubles (22nm)
：α- & β- tubulin
subunits：
(throughout the cell, but concentrated around nucleus)
mitosis時時, microtubules 會 highly organized & help
the separation of chromosomes (可能可能provide
可能 motive
force)
chap 1.1 to 1.2 43

Microtubules
+ e.g. cilia
kinesin
flagella beating motion
dynesin
+
ATP

move organelle along microtubules (以以1μμm/s移動

移動)
移動
e.g. reason： ：
•contraction of muscle myosin, kinesin,dynesin
propelling action of cilia
and flagella splitting “ATP”
• intracellular transport
of organelles driving sliding motion along
chap 1.1 to 1.2
microtubules and 44
microfilaments

22
 chap 1.1 to 1.2

：
(3)Intermediate filaments (8-10nm)：
provide internal mechanical support for the cell and
to position its organelles
subunit：： vimentin, keratin,desmin等
等
e.g. 在endothelial cells(內皮細胞
內皮細胞),
內皮細胞 vimentin
fibers anchor nucleus and fat droplets in
the specific location

• The cytoplasm is crowded, highly organize and dynamic!!

• Cytoplasm：：
meshwork of structural fibers (protein fibers)
membrane-bound organelles locate在其中在其中
chap 1.1 to 1.2 45

Endocytosis and Exocytosis carry traffic across

the plasma membrane
胞飲)：
胞飲 ：
Endocytosis(胞飲
A mechanism for transporting components of the
surrounding medium deep into the cytoplasm
吞噬)：
吞噬 ：
Phagocytosis(吞噬
One kind of endocytosis， ，but carry cell fragment or
other smaller cells
胞吐)
胞吐 ：
Exocytosis (胞吐
A vesicle in the cytoplasm moves to the inside surface
of the plasm membrane fuses with it, then release the
contents outside the membrane

chap 1.1 to 1.2 46

23
 chap 1.1 to 1.2

Cells Build Supramolecular Structures

：
(A)Protein：

種amino acids as building blocks

20種

chap 1.1 to 1.2 47

Cells Build Supramolecular Structures

：4 possibilities
(B)DNA：

5’ 3’

chap 1.1 to 1.2 48

24
 chap 1.1 to 1.2

(C)Lipids
Glycerol

+ Fatty acids
e.g. Oleate
palmitate

R1

可形成
R2
Lipid bilayer

chap 1.1 to 1.2 R3 49

(D)Polysaccharides
：starches, glycogen and
Most abundant polysaccharides：
cellulose
Monomeric subunit： ：主要為glucose
主要為

chap 1.1 to 1.2 50

25
 chap 1.1 to 1.2

Structural hierarchy in the molecular organization of

cells

chap 1.1 to 1.2 51

Structural hierarchy in the molecular organization of cells

Cell
Nucleus
Mitochondria
Organelles Golgi body
E.R
etc Membranes
Supramolecular assemblies Ribosomes
Non-covalent interactions Chromatin
Hydrogen bond Microtubules
Ionic interaction
Hydrophobic interaction
Van der Waals forces Proteins
Macromolecules DNA
RNA
Polysaccharides
Covalent bonds Amino acids
Building blocks Nucleotides
chap 1.1 to 1.2 52
Sugars

26
 chap 1.1 to 1.2

1.2 Chemical Foundations

Complexity of life Simplicity of “element”world

Bulk elements： ：required in gram(only H, C, N, O, Na,

P, S, Cl, K, Ca, in red) 佔99%
Trace elements：
chap 1.1 to 1.2
：required much less (colored in yellow)
53
如Mg, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Se, Mo, I

Covalent bonding 組成biomolecule的骨架

組成 的骨架
H O
H H
O H H O
C H S H
O H
H N P
O
H H H H H
Geometry of
Carbon Bonding

C C
Bond length
1.54A

chap 1.1 to 1.2 54

27
 chap 1.1 to 1.2

Biomolecules Are Compounds of Carbon

with a Variety of Functional Groups

Some common functional

groups of biomolecules
e.g. glycine(R=H)
Many biomolecules Multi-functional
“reactivity (chemical properties) of
biomolecules determined by: (1) functional
groups, (2) 3-dimensional structure carboxyl
chap 1.1 to 1.2 55
amino

chap 1.1 to 1.2 56

28
 chap 1.1 to 1.2

Cells contain a universal set of small

molecules
• In cytosol:a collection of a thousand of small
molecules (Mr ~ 100 to 500), the central
metabolites in the major pathway in cells.
• including amino acids, nucleotides, sugars, etc.
Polar or charged, in µM to mM
• may contain secondary metabolites (in specific
plant cells that gives plants characteristic scents,
e.g morphine, caffeine etc)

chap 1.1 to 1.2 57

Macromolecules Are the Major Constituents of Cells

Proteins and nucleic acids are informational

chap 1.1 to 1.2 58
macromolecules

29
 chap 1.1 to 1.2

Three-Dimensional Structure Is Described

by Configuration and Conformation
：
Three ways to represent the structure of Biomolecules：

(a) Structure Formula

(b) Ball-and-stick model (shows relative bond length and
bond angles
(c) Space-filling model (shows correct 電子密度的bond
電子密度的 length)
chap 1.1 to 1.2 59

Configuration －changed only by bond-breaking

Configuration ：fixed spatial arrangement of atoms in a
molecule

In the presence of (1) double bonds (2) chiral center

chap 1.1 to 1.2 60
configurational isomers

30
 chap 1.1 to 1.2

respected to geometric
double bond isomers
or cis-trans
R/S form
stereoisomers
chiral centers D/L form
enantiomers (mirror images)

diastereomers (non-mirror images)

n 個 Chiral carbons 2n個 stereoisomers

Configurational isomers can be isolated (if use proper
separating methods)
有chiral center， ，表四個不同的atom，
表四個不同的 ，C的四周圍電子密度不
的四周圍電子密度不
均勻，
均勻，使電磁波偏移
• Enantiomers will notate the plane of plane-polarized light
• Racemic mixtures(equimolar mixture of two enantiomers)
will
chap 1.1 not
to 1.2 rotate the plane-polarized light 61

Molecular Conformation is Changed by Rotation

about Single Bonds
Molecular conformation

The spatial arrangement

of substituent groups can
be changed by “free
rotation”(w/o any bond
breaking)
See figure 1-21
Potential energy differences of
many conformations of ethane
Energy differences are two
Cannot be separated
small conformational isomers
chap 1.1 to 1.2 62
can be interconverted

31
 chap 1.1 to 1.2

Configuration and conformation define biomolecular

Structures
：related to their three-dimensional
Molecular recognition：
結構上的互補性,
結構上的互補性 complementarity)
structures (結構上的互補性
e.g. Hormone molecule with receptor
Antigen with a specific antibody
Substrate with the catalytic site of an enzyme

Example: Fig. 1-22

TAR region of HIV

genome w/arginine
chap 1.1 to 1.2 63

Interactions between Biomolecules are stereospecific

In vivo, biomolecules are usually present in only one

of their chiral forms.
e.g. Amino acids Only L isomers
Glucose Only D form

Enzymes have the ability to distinguish between

！)
isomers. (Enzymes are stereospecific！
Example: Fig. 1-23

chap 1.1 to 1.2 64

32
 chap 1.1 to 1.2

：
(a)Carvone：
Smell as spearmint (R form)
香菜 (S form)
caraway香菜
Smell sensory receptor can
！
distinguish！

：
(b) aspartame：
Taste sweet aspartame
！
taste receptor can distinguish！
chap 1.1 to 1.2 65

33