Cytoplasm 2 and 3

MLS 407 | Human Histology

Prelim | 1st Semester

CYTOPLASM 2
Cell Membrane
 Does not paly an active role in
transporting the substance
 Plays an active role in transporting a
substance from outside the cell towards
its cytoplasm Phagocytosis – if the material that is engulfed
 Will engulf the material that is supposed and enclosed in the vesicle is solid particle such
to be transported towards the cytoplasm as bacteria and yeast.
and the material will now be enclosed in
a vesicle Pinocytosis –“cell drinking”, because the
material that is engulfed and enclosed in the
Portion of the membrane forms the vesicle vesicle is fluid by nature

Receptor mediated endocytosis – the material is

only enclosed in the vesicle if the material will
bind to the receptor

1. Phagocytosis – White blood cells

(neutrophils and macrophages) take up solid
materials
Endocytosis  Engulfment of bacteria, protozoa,
 One of the ways on how the cell can dead cells and unneeded
transport chemicals from external extracellular constituents
environment towards its cytoplasm
 Its difference from the passive active
transport is in endocytosis the material
will end up being enclosed in a vesicle
derived from the portion of the cell
membrane that surrounded or engulfed
the material
 Cellular process in which substances are
brought into the cell.
 The material to be internalized is
surrounded by an area of cell membrane,
which then buds off inside the cell to
form a vesicle containing the ingested
material

Brown – bacterium
1. Chemotaxis and adherence of microbe
to phagocyte
 2. Ingestion of microbe by phagocyte
3. Formation of a phagosome
4. Fusion of the phagosome with a
lysosome to form a phagolysosome
5. Digestion of the ingested microbe by
enzymes
6. Formation of residual body containing
indigestible material
7. Discharge of waste material

A part of that cell membrane of the phagocyte

will invaginate to enclosed the bacterium. A
portion of the cell membrane will detach from
the cell membrane and will form a vesicle.
Inside the vesicle, internalized or engulfed is the
bacterium, forming phagosome (product of
phagocytosis)

Phagosome – does not have the ability to kill the

 The phagocytosed material is then
bacteria. It fuse with other organelle with
enclosed in a phagosome
digestive enzymes. Phagosome will fuse with
 Digestion starts after the fusion of the
the lysosome forming phagolysosome. The main
phagosome with lysosome to form
purpose of this is to expose the engulfed
phagolysosome
bacterium to the powerful digestive enzyme of
the lysosome

If bacterium is placed directly to the cytoplasm

of the cell, the bacterium will die within 10
second because the cytoplasm contains enzymes
that could attack the bacterium. So why is the
bacterium contained within phagosome when the
cytoplasm can kill it in 10 seconds?
There are bacteria that can produce toxins, if we
allow bacteria to be exposed to the cytoplasm
they might release toxins that can kill the 2. Pinocytosis
phagocytes. For the phagocytes protect  Fluid-phase endocytosis
themselves from the toxin, the bacteria should  “Cell drinking”
be enclosed in a vesicle. By this the toxin will be  Small invaginations of the cell
enclosed in the phagosome. membrane form and entrap fluids
which are then enclosed in vesicles.
Chemotaxis
Transcytosis
 (engulfed, not metabolized, transferred
to the other side of the cell)
 Similar to pinocytosis but does not
result to the metabolism of the engulf
fluid or substance
IgG - fluid
When we are born, we don’t have our own
antibodies because we cannot produce them, the
immune system is still immature.
The first 6 months of a baby is being protected
by the antibodies of the mother that was
transferred through transcytosis.
3. Receptor-Mediated Endocytosis
 Binding of ligand/target molecule to
the receptors will cause widely
dispersed receptors to aggregate
which results to the take up of the
ligand
LDL – carried cholesterol towards the cell of the
body
 LDL is rich in cholesterol
 Rich in cholesterol
 Has ApoB-100
 Considered to be the bad cholesterol
 If you have it in excess it will eventually
cause the deposition of high amounts of
cholesterols to the walls of the arteries
causing the formation of atherosclerotic
plaque
ApoB-100
  Used by the ldl particle to bind to the ldl
receptor cell, will cause the Clathrin and adaptin aggregate on the
internationalization of the ldl particle by cytoplasmic side
the cell  Responsible for the invagination of the
cell membrane cause the formation of
Familial hyper cholesterol limia the vesicle
 A condition characterized by the
absence or reduced expression of the ldl
receptors on the surface of the cell
 If there is no ldl receptor, the ApoB-100
have no receptor to bind to ldl will
remain in the blood causing now high
ldl in the blood causing possibility of
deposition of cholesterol to the walls of
the artery. People born with this
condition will eventually die early
because of heart attack and stoke Dynamin helps mediate the liberation of the
clathrin-coated vesicle from the plasma
membrane
 Cause the vesicle to detach form the rest
of the cell

Vesicle is then transported towards the early

endosomes

1. Ligand binds to membrane receptor

2. Receptor-ligand migrates to clathrin-
coated pit
3. Endocytosis
4. Vesicle loses clathrin coat
5. Receptors and ligands separate
6. Ligands go to lysosomes or Golgi for
processing
7. Transport vesicle with receptor moves to
the cell membrane
8. Transport vesicle and cell membrane
fuse (membrane recycling) Complete the sentences: Endocytosis
1. Ligand binds to Receptor. Receptors
During endocytosis, receptors upon binding to aggregate as well as clathrin and
the target substance accumulates in a specific adaptin.
region of the membrane 2. Dynamin causes the vesicle to detach
from the cell membrane
There are also other proteins that will aggregate 3. Vesicle is then transported to early
on the cytoplasmic side of the cell membrane. endosome.
These are clathrine and
Adaptin. Endosomes
  Will cause the detachment of the
receptor and the ligand/target molecule
 Cause the vesicle with the receptor to
detach from itself, the cell membrane
and that vesicle with the receptor will
eventually be recycled back to the cell
membrane to pick up another target
molecule
During endocytosis, part of the membrane
becomes part of the vesicles. During exocytosis,
the membrane is returned to the cell surface.
Endosomes
 Membrane bound organelles associated
with the endocytotic pathways
 Sort out and recycle proteins
internalized from the endocytotic
pathways
Endosomes sort out endocytosed materials
Early endosome – will determine what will the
cell do with endocytosed particle
Two types of endosomes:
1. Early endosome – found near the cell
membrane, first to interact with the
endocytic vesicle
2. Late endosome – found deeper than the
early endosome; receives the vesicles
originating from the early endosome
a. Matures into lysosome, thus
called prelysosome
According to Paulina:
2 models on the existence of the early and late
endosomes (not yet proven which is true):
1. The early and late endosomes are two
different organelles existing on the
cytoplasm of the cell. Late endosome
received the processed material coming
from early lysosome
2. The late endosome is the mature form of
the early endosome. After the early
endosome, it will process the endocytose
material to form the late endosome.
Late lysosome will eventually form
lysosome, that is why it is called pre-
lysosome
Fusing of vesicle with the early lysosome. There
is a portion in the early lysosome that transports
hydrogen towards the internal component. As
the particle is transferred from early endosome
to the multivesicular body (buds off) to the late
endosome the organelles or structure will
accumulate hydrogen in their internal
compartments. The accumulation of the
hydrogen from the early endosome to
multivesicular body and to the late endosome
will acidify the environment.
As the late endosome will mature to form the
lysosome, the acidification of the internal
compartment of the organelles still continuous.
  Site for intracellular digestion and
turnover of cellular components
 Contains different powerful digestive
enzymes
 Mature form of the late endosome
 Will destroy and digest the organelle
using the same powerful digestive
enzymes (proteins)

Prohydrolase enzymes are produced from the

Rough Endoplasmic reticulum

Enzymes, using their signal patch, binds to

Mannose-6- phosphate

Enzyme and M-6-P binds to M-6-P receptors in

early and late endosomes which cause them to
be internalized. Further processing causes them
to become active hydrolases

Take note of the changes in the pH inside the

endosome

- Enzymes of the lysosomes are produced

in the rough endoplasmic reticulum
1. Enzymes are produced in the Rough
endoplasmic reticulum. When enzymes
pH level:
are newly-produced, they are immature
 Early endosome – 6.5 and non-functional, that is why the
 Multi-vesicular – 5.5 enzymes are transported to the Golgi
 Late endosome – 4.5 apparatus
2. Golgi apparatus is known to modify
Lysosomes stored package and transport proteins
and enzymes. Inside the Golgi apparatus
 the enzymes of the lysosome are bound
to Mannose-6- phosphate.
3. Enzyme and Mannose-6- phosphate will
bud off from the Golgi apparatus and be
transported to the early and late
endosomes
The purpose of the incorporation of the
enzyme and Mannose-6- phosphate is
for the enzyme to be engulfed
internalized by the Mannose-6-
phosphate receptor in the early and late
endosome
1. Inner membrane
o Had folded areas called cristae
2. Outer membrane
Intermembrane space – the space between the
inner and outer membrane
Mitochondrial matrix (or matrix) – the space
within the inner membrane
Cristae – increase the areas surface area for
energy production
Mitochondria
 Inner membrane is folded into cristae
which project into matrix and greatly
increase membrane's surface area

Mitochondrion under electron microscope

The unwanted damaged and non-functional

organelles need to be removed from the cell.
These organelles are enclosed in a vesicle, and
the vesicle will be called autophagosome
Autophagosome will fused with lysosome. If
lysosome is used by the cell to remove its own
organelle or other components, this process id
called Autophagy

Mitochondrion

Mitochondria
 Membrane-enclosed organelle that
functions for ATP production
 Responsible for the synthesis of ATP
Has two membrane:
All cells in the body have the same types of
organelles but they differ in terms of the number
of the organelles in their cytoplasm

Mitochondria are abundant in the following

cells:
1. Cardiac muscle – it needs to work every
second of the day to help the heart pump
out the blood for the blood to
continuously circulate all throughout the
body to distribute oxygen and nutrients
2. kidney tubules – always functioning to
adjust to the concentration of urine
Mitochondria
3. Sperm cell – the mitochondria will
 Highest in number in cardiac muscles
provide energy to the flagellum so that
and kidney tubules
the flagellum can make the sperm cell
 Also concentrated in areas in the cell
move forward or to propel the sperm
where energy is needed (midpiece of
cell forward, so it can reach the egg cell
sperm cell)
Mitochondria are found almost in all of the cell
in the body except the white blood cells but the
number of mitochondria will differ.

Midpiece – connects the flagellum to the head of

the sperm cell
- Since there is abundance of
mitochondria, it will now provide
energy to the sperm cell

Review of biochemistry
The mitochondrion functions to produce atp and
most of the time ATP is produced from glucose

ATP can be derived from a lot of things but the

most common source is glucose.
As the glucose enter the cell, the glucose will
undergo glycolysis in the cytoplasm.
Glycolysis takes place outside the
mitochondrion, in the cytoplasm.

Glucose is converted to pyruvate.

After the pyruvate is produced in the process of

glycolysis, the pyruvate will enter the
mitochondria and inside the pyruvate will be
converted into Acetyl coenzyme A. This is
where the part of the mitochondrion need the
production of ATP will start.

The acetyl coenzyme A will participate in the

Kreb cycle and the products of the kreb cycle
will eventually participate or will become part of
the electron transport chain.
The site for Kreb’s cycle or the citric acid cycle
is the mitochondrial matrix

 Glucose enters the cell through the action of

insulin
 Glucose undergoes glycolysis in the
cytoplasm to produce pyruvate
 Pyruvate enters the mitochondria and is
converted into Acetyl Coenzyme A
 Acetyl CoA enters Kreb’s cycle
(mitochondrial matrix)
 FADH2 and NADH are products of Kreb’s
cycle
 They enter the electron transport chain in the
inner membrane
Nadh and fadh two will interact with the
proteins of the electron transport chain and the
main end point is to release or to transport of
hydrogen from the matrix into the
intermembrane space

 FADH2 and NADH will interact with the

proteins of the electron transport chain and
transfers hydrogen in the intermembrane
space
o Hydrogen ions will accumulate in
the intermembrane space, there is
now an imbalance in the distribution
of hydrogen within the
mitochondrion
o The hydrogen ions will be
transported back to the
mitochondrial matrix
 Hydrogen ions enter through the ATP
synthase complex resulting to production of
ATP
o Every time that hydrogen ion will
pass through the ATP synthase, you
will now have the production of
ATP
 The set of the DNA in the mitochondrion is
present in the mitochondrial matrix
Nucleus - Control center of the cell because it
contains the dna

The mitochondria does not rely on the nucleus

for the production of their proteins because it
also have their own sets of DNA.

Some of the proteins present in the

mitochondrion are still encoded in the nucleic
acid found in the DNA
Endosymbiotic theory
Mitochondria - Theory on why mitochondria has its
 The mitochondrial matrix also contains own set of DNA
a small circular chromosome of DNA - Suggests that mitochondria were
and sets of mRNA formerly a separate living organisms
- Mitochondria is formerly a bacteria that
was failed to be killed
There is more to mitochondria than just the
powerhouses of the cell!

Other functions of the mitochondria

(1) Synthesis of steroid hormones
(2) Beta oxidation of fatty acids – for
energy production
(3) Initiator of apoptosis
(4) Synthesis of reactive oxygen species
(1) Synthesis of steroid hormones
o Derived from cholesterol
o Synthesized in the mitochondria of the
cells
1. Cholesterol enter the mitochondria
2. Processed in the mitochondria
3. The products of converted cholesterol
are steroid hormones
(2) Beta oxidation of fatty acids – for energy
production
o Fatty acids are broken down into the 2-
carbon compound acetyl-CoA for
energy production
o Fatty acid needs to undergo beta
oxidation to be converted to energy

Stress-eating
Cholesterol
- Four fused ring, the
hydrocyclopentanophenanthrine ring
and the hydroxyl group
Testosterone, cortisol, estrogen, and aldosterone
share the same chemical structure

Mitochondria: Steroid hormone synthesis

In stress-eating, you are overloading you body
with excessive glucose, some glucose will be
converted to ATP by the cells in the body, some
will be stored in the liver and skeletal muscle in
the form of glycogen, but the excess glucose will
be transported into adipose cells

Once the glucose molecules are in the cytoplasm

of the adipose cells, theses glucose molecules
will be converted to fatty acids and the fatty
acids will become a part of the triglyceride.
These will now be stored in the cytoplasm of the
adipose cells causing the cells to become large
making you gaining weight

Balik-alindog program

Beta-oxidation of fatty acids

In this case your body will run out of glucose to
be used up a source of energy, so that your body
will look for alternative sources, your body will
break down the stored fats in the adipose cells,
the triglyceride will be released in the blood.

Fatty Acid

Should the body undergo starvation or fasting,

the fats in the adipose cells will be broken down
and there would be a subsequent release of fatty
acids in the blood and these fatty acid in the
blood will be distributed to the liver for the fatty
acid to undergo beta-oxidation.
Fatty acid – long hydrocarbon chains with
carboxylic acid group in the terminal end
Removal of 2carbon = acetyl-CoA

Fatty Acid (3) Initiator of apoptosis

o Mitochondria are sensitive to trauma or
injury thus can initiate the cell to die by
releasing chemicals that initiate
programmed cell death

1. Removal of carboxylic group to form

the acetyl coenzyme A
2. Removal of 2 carbon chain to undergo
beta-oxidation again

Beta-oxidation of fatty acids

Apoptosis = programmed cell death

Mitochondrion is a killer

Appreciate that Acetyl-CoA enters Kreb cycle to

form ATP

(4) Synthesis of reactive oxygen species

 o Products of the chemical modification of
oxygen
o Reactive oxygen species such as
superoxide and hydrogen peroxide can
kill bacteria
ROS are produced during the electron transport
chain
One of the products is the conversion of oxygen
into hydrogen peroxide (bacteria killing)
Mitochondrion: Synthesis of reactive oxygen
species
The mitochondrion can provide the cell with
reactive oxygen species in the form of
superoxide and hydrogen peroxide because of its
electron transport chain.
Reactive oxygen species can have anti-microbial
effects, the superoxide and hydrogen peroxide
can be utilized by cells, particularly phagocytes
to kill bacteria.
Hydrogen peroxide is potentially damaging to
the organelles
Peroxisomes
(1) Contains CATALASE enzyme which
breaks down Hydrogen peroxide into
water
Mitochondria: beta oxidation of fatty acids
- Can only work on medium and long
chain fatty acids
Mitochondria is not capable of facilitating the
beta oxidation of very ling chain of fatty acids (2) Peroxisomes are also involved in beta
(more than 18 hydrocarbon) oxidation of VERY LONG FATTY
ACID chain
Medium and long chain Very long chain fatty a. >18 carbons
acids b. Energy production through
acetyl-CoA
(3) Synthesis of plasmalogen for the
synthesis of myelin sheath

Acted upon by the enzyme

phenylalanine hydroxylase
2. Converted into L-tyrosine (amino acid)
– will serve as a substrate for the
production of the brown pigment
Made possible by the enzyme phenylalanine
hydroxylase
CYTOPLASM 3
Physical traits are affected by the set of proteins
Physical traits
we have in our body
 Differences in height
o Growth hormone (protein)
 Difference in skin color
o Melanin

Synthesis of Melanin

Growth hormone and PAH are Proteins

 Proteins are made of specific sequence
of amino acids
 Example Protein A

1. L-phenylalanine (an amino acid)


  Protein B


 Protein c

If you would not produce phenylalanine

hydroxylase you will appear lighter and vice-
versa

Changing one amino acid will cause the protein

to become another protein

If the sequence of the amino acid is not followed

it will form another protein Blue arrow = double stranded DNA
Red arrow = ribosomes (site for site for protein
synthesis)

Gene is found in the nucleus

The site for protein synthesis (ribosome) is in
the cytoplasm

The DNA is enclosed within the nucleus, for it

to be protected from the damaging effect of the
enzymes or chemicals in the cytoplasm
Gene will determine the proper sequence of
amino acid

Transcription
 Unwind the portion of the DNA
containing the gene, then make a
complimentary copy of the sequence of
the bases in the gene. The copied form
of the gene is now messenger RNA
(mRNA)
  DNA (gene) is transcribed in the form of
mRNA in the nucleus
 The mRNa will now be the one that will
go out of the nucleus and interact with
the ribosomes to encode the sequence of
the amino acid to form the specific
protein that is encoded by the gene that
was copied in the DNA inside the
nucleus

Process involve in production of proteins:

TRANSCRIPTION
- Gene in DNA is copied in the form of
messenger RNA (mRNA)

TRANSLATION
- mRNA codes are read in the ribosomes
for protein synthesis

Rough and Smooth Endoplasmic Reticulum

As can be seen in the picture, there is the
unwinding of the DNA and one of the
complimentary because most likely that strand
us the one that contains the gene important for
the production of the protein.

The strand is complimentarily copied to form the

red ribbon-like mRNA and the mRNA will now
go out of the nuclear pore then into the Endoplasmic Reticulum
cytoplasm and will interact with the large and Two types:
small subunits of the ribosome. The code copied 1. Rough Endoplasmic Reticulum
by the mRNA from the DNA will now be read  with ribosomes
by the ribosomes and they will now be translated  functions to produce proteins
to form the correct sequence of amino acid to  continuous with nuclear
form the appropriate protein membrane
2. Smooth Endoplasmic Reticulum
 Devoid of ribosomes

The outer nuclear membrane is directly

continuous with the organelle rough
endoplasmic reticulum
Take note of the extension of the nuclear
membrane into the Rough ER

Rough ER is continuous with outer nuclear

membrane

Yellow = nucleolus
Red = outer and inner nuclear membrane
Green = mitochondrion
Endoplasmic reticulum : Cisternae
Blue = rough endoplasmic reticulum
Cisternae – series of interconnected sacs found
within the endoplasmic reticulum
- Foldings within the inner mitochondrial
membrane

Cistern of RER = saccular

Cistern of SER = tubular

All proteins except antibodies are produced in

the liver, expect an abundant number of rough
endoplasmic reticulum
Functions of the SER

1. Lipid synthesis – adipocytes

o There is high amount in adipose
cells
2. Drug and alcohol metabolism - liver
3. Sequester Calcium in the muscles
(Sarcoplasmic reticulum)

Drug metabolism
Two phases:
1. Phase 1
 Involves enzyme called
cytochrome p450
Every time that we will take in alcohol or 2. Phase 2
ethanol. The ethanol will be metabolized in the
liver to form the acetaldehyde.

If the you drink more alcohol will happen, the

cytoplasm and cytosol will be overwhelmed by
the alcohol and the cytoplasm and cytosol will
call for back up – smooth endoplasmic reticulum

3. Sequester Calcium in the muscles

(Sarcoplasmic reticulum=ser)

Nerve is trying to control the muscle. The nerve
does it by releasing acetylcholine the release of
acetylcholine neurotransmitter activated an
action potential.
Th action potential will activate the organelle
sarcoplasmic reticulum.
After being triggered by the action potential, this
sarcoplasmic reticulum will release the stored
calcium and that will now cause the muscle to
contract.
Should the muscle undergo relaxation, the
calcium will now be re-sequestered or restored
in sarcoplasmic reticulum
 Proteins produced by the RER are initially
immature and nonfunctional….
 THUS, they need to be further processed…
Golgi Apparatus
 Modifies, store and package proteins
synthesized from the RER
 Golgi apparatus also determine where
the protein is transported.
 Set of membrane bound sacs called
cisternae
o Has cis face - which faces the
rough ER
o Has trans face - where the
packaged proteins exit out
Constitutive versus Regulated Secretory
pathway
Pathways are associated with the golgi apparatus
with how the golgi apparatus will transport
mature proteins
Constitutive pathway
 proteins are packed into transport
vesicles and constantly released outside
the cell
 No need to for any stimuli
Regulated pathway
 proteins are packed into secretory
vesicles and then temporarily stored
 Only released with the presence of
stimuli
 Fate of proteins synthesized by RER
 Anterograde/Forward pathway – Protein
goes to Golgi apparatus then transported
elsewhere
 Retrograde pathway – proteins are
returned back to RER from Golgi
apparatus

Anterograde/Forward pathway
- The protein will be synthesized in the
ribosomes of the RER then the protein
will be transported to the golgi apparatus
for modification, for packaging, storing.
The arrival of the action potential or nerve Then after, the proteins will become
impulse (postsynaptic neuron) will cause the functional and mature the proteins will
calcium to go outside and this calcium ion will bud off from the trans face of the golgi
cause the vesicles containing acetylcholine to apparatus. The protein will be
fuse with the postsynaptic neurons membrane to transported outside the cell.
release acetylcholine.
The vesicles are not moving, they are not fusing
with the membrane not unless there is a presence
of the calcium ion.
The calcium ion acts as the stimulus, without it
the vesicle will remain still and not fuse with the
postsynaptic neurons membrane

Retrograde pathway
 - The protein produced from the RER is
then transported to the golgi apparatus
for modification, processing, and storing
but after the proteins will mature and
they will bud off from the trans face of
the golgi apparatus. They will be
transported back through RER.
- RER also needs proteins for it to
function. It can produce proteins but the
proteins produced by it is not yet
mature, so it needs to be processed in
the golgi apparatus for it to mature and
functional, and transported back to the
RER.
Coatomers
 Protein complex that coats membrane-
bound transport vesicles.
 Two types of coatomers are known:
o COPI (retrograde transport from
trans-Golgi network to cis-Golgi
network and endoplasmic
reticulum)
o COPII (anterograde transport
from ER to the cis-Golgi)

 Cylindrical structures
 Composed of rings of proteases
enzymes
 Each end of the structure recognizes
proteins with ubiquitin attached
o Ubiquitin – protein present in
the cytoplasm of the cell and its
main key role is to look for any
misfolded and denatures
proteins
 Proteins in the cytoplasm are not
immediately targeted by the proteasome
not unless they are bound to ubiquitin
 Terminal ends of the proteasome
recognized ubiquity
 If the protein has a ubiquitin conjugated
to it, the protein will now be targeted by
the proteasome and the protein will be
broken down into amino acid

The golgi apparatus and RER has a chance to 

produce misfolded or non-functional proteins.
So what are the ways to get rid of these proteins

Proteasomes
 Small abundant protein complexes
present in the cytoplasm
 Degrades denatured, non-functional Proteasomes and Ubiquitin
polypeptides
 Remove proteins no longer needed by
the cells
Centrioles
 Function to produce the mitotic spindle
fiber that are very important in mitosis
and meiosis
 Two nonmembranous cylindrical
structure composed of microtubules
 Composed of 9 triplets of microtubules


 Composed of one pair which are
arranged at right angle with each other
 Centrioles produce the mitotic spindle
fiber during cell division