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01
JUNE 14, 2013
Cell and Cell Membrane: A Biochemical Approach
Allan L. Hilario, M.D.
INTRODUCTION
Cell Phylogeny
Key Concept: Grouping organisms according to common properties implies
that a group of organisms evolved from a common ancestor.Based on the
similarities in ribosomal RNA, living organisms are classified into 3 domains.
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Transcribers: Aclan, J.V., Advento, V., Bolos, C.,Cabiscuelas, Y.N., Cuaderno, C., Gamboa, K.A., Javier, K., Laurilla, L.B., Rodenas, E., Roxas, F.
BIOCHEMISTRY Cell and Cell Membrane: A Biochemical Approach
Gluconeogenesis Cytoplasm of
hepatocytes, renal cells
and in special condition
the intestinal cells
Replication Nucleus
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Transcribers: Aclan, J.V., Advento, V., Bolos, C.,Cabiscuelas, Y.N., Cuaderno, C., Gamboa, K.A., Javier, K., Laurilla, L.B., Rodenas, E., Roxas, F.
BIOCHEMISTRY Cell and Cell Membrane: A Biochemical Approach
Cytoskeleton
- network of protein scafolding which
mainatains cell’s shape and serves as
tracts for organellar movement.
- assembles as polymers from protein
subunits.
- 3 types of protein filaments:
a. Microfilaments (6–8 nm)
- Actin is the protein component of the Plant alkaloids:
microfilaments. Vinblastine- vinca alkaloid; acts in G & S
- 2 forms of actin: phases by inhibiting microtubule
G-actin (globular) formation, inhibits DNA/RNA synthesis;
Monomolecular form antineoplastic
Vincristine- vinca alkaloid; acts in M & S
asymmetrical molecule with a mass of
phases by inhibiting microtubule
42 kDa, consisting of two domains. formation, inhibits DNA/RNA synthesis;
F-actin (filamentous) antineoplastic.
Polymer form Colchicine- disruption of cytoskeletal
functions through inhibition of β-tubulin
polymerization into microtubules which
prevents activation, degranulation, and
migration of neutrophils thought to
mediate some gout symptoms;
antigout(acute gout).
Paclitaxel (Taxol)- natural taxane, prevents
depolymerization of cellular microtubules,
which results in DNA, RNA, and protein
synthesis inhibition’ antineoplastic
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Transcribers: Aclan, J.V., Advento, V., Bolos, C.,Cabiscuelas, Y.N., Cuaderno, C., Gamboa, K.A., Javier, K., Laurilla, L.B., Rodenas, E., Roxas, F.
BIOCHEMISTRY Cell and Cell Membrane: A Biochemical Approach
Mitochondria
- compose the 1% DNA of the cell rERcis-Golgi network cisternae trans-Golgi network
cell exterior
- evolved from the “Endosymbiosis Theory”
Function:
Function:
- Production of energy (ATP)
- modification, sorting, and packaging of proteins and other
- Some processes occurring within the mitochondria:
materials
- Electron transport chain and oxidative phosphorylation
- Urea cycle
- Tricarboxylic acid cycle/Citric acid cycle/Kreb's cycle Vesicular organelles
- ß oxidation in animal cells Lysosomes
- ketogenesis -common in animal cells but rare in plant cells
Functions:
Endosymbiosis Theory - contain hydrolytic enzymes necessary for
Key concept: The endosymbiosis theory explains the origin of intracellular digestion
mitochondria and chloroplasts and their double membranes. This - get rid virus and bacteria, digest food particles and
concept postulates that chloroplasts and mitochondria are result of other damaged organelles
years of evolution initiated by the endocytosis of an aerobic Peroxisomes
bacteria and blue-green algae. With this theory, an accepted Functions:
mechanism on how eukaryotic cells evolved from prokaryotic cells - involve in the breakdown of very long chain fatty
is explained. acids
- contain the enzyme catalase which decomposes the
toxic hydrogen peroxide
Secretory vesicles
Function:
- transport substances to the cell surface for release
Cell Membrane
Endoplasmic Reticulum Fluid Mosaic Model (Singer and Nicolson) – according to this model, the
- network of tubules and flattened sacs that serve a variety
molecular arrangement of plasma membrane resembles a continually
of functions in the cell
moving sea of fluid lipids that contains a mosaic of many different
proteins.
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Transcribers: Aclan, J.V., Advento, V., Bolos, C.,Cabiscuelas, Y.N., Cuaderno, C., Gamboa, K.A., Javier, K., Laurilla, L.B., Rodenas, E., Roxas, F.
BIOCHEMISTRY Cell and Cell Membrane: A Biochemical Approach
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Transcribers: Aclan, J.V., Advento, V., Bolos, C.,Cabiscuelas, Y.N., Cuaderno, C., Gamboa, K.A., Javier, K., Laurilla, L.B., Rodenas, E., Roxas, F.
BIOCHEMISTRY Cell and Cell Membrane: A Biochemical Approach
The lipid bilayer of the cell membrane has the ability to reseal after a
small disruption through lateral diffusion of its lipid component. Larger
tear due to mechanical stress is an energy-requiring process through
Ca2+- dependent process similar to exocytosis-like process.
[emphasized in the lecture]
The cell membrane has different composition of lipid and protein in its
outer and inner leaflet of the lipid bilayer.
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Transcribers: Aclan, J.V., Advento, V., Bolos, C.,Cabiscuelas, Y.N., Cuaderno, C., Gamboa, K.A., Javier, K., Laurilla, L.B., Rodenas, E., Roxas, F.
BIOCHEMISTRY Cell and Cell Membrane: A Biochemical Approach
The lipid composition of the bilayer is asymmetric, with a higher content 2. Caveolae – invaginations of lipid rafts by the action of caveolin.
of phosphatidylcholine and sphingomyelin in the outer leaflet and a Important in membrane breakage and sealing.
higher content of phosphatidylserine and phosphatidylethanolamine in
the inner leaflet. Phosphatidylinositol which can function in the transfer CELL MEMBRANE TRANSPORT
of information from hormones and neurotransmitters is also only found - the transfer of solutes and information across membranes
in the inner leaflet. [Lieberman and Marks, 2009]
TYPES OF CELL MEMBRANE TRANSPORT
a. Cross-membrane movement of small molecules
CELL MEMBRANE PROTEINS a. Diffusion (Passive and Facilitated)
b. Active Transport
b. Cross-membrane movement of large molecules
(Endocytosis and Exocytosis)
c. Signal transmission across membrane
a. Cell surface receptors
1) Signal transduction (e.g. glucagon ->cAMP)
2) Signal internalization (coupled with endocytosis
eg LDL receptors, Insulin and Glut transporters)
b. Movement to intracellular receptors (steroid hormones, thyroid
hormones, retinoids, Vit. D)
d. Intracellular contact of Communication
A. PASSIVE TRANSPORT
- transport that do not require energy
-movement of solute from an area of HIGH CONCENTRATION to an area
of LOW CONCENTRATION
-depends on concentration gradient; creation depends on
1. chemical gradient
-difference of solute concentration or its ratio C 2 /C1
2. transmembrane electrical gradient (Vm in millivolts).
Types of Membrane Proteins -Solutes follow the 2nd law of thermodynamics where it tends to assume
spontaneously the greatest randomness and the lowest energy
Integral proteins Peripheral proteins
Have alpha-helical structure (with Have amphiphatic alpha-helical 1. Simple diffusion
15-20 amino acids that have bulky structure - without membrane protein
side-chains) movement of solutes down its electrochemical gradient due
Interact intensively with the Do not interact directly with the torandom thermal movement or simply because the solute is
phospholipids (require the use of hydrophobic cores of the permeable through the lipid bilayer because it is small enough
detergents of solubilisation) phospholipids in the bilayer and/or hydrophobic.
Removable only by agents (e.g. Removed by relatively mild 2. Facilitated diffusion
detergents, organic solvents) that treatments that interfere with movement of solutes down its electrochemical gradient
interfere with hydrophobic electrostatic interactions or through either transporters or ion channels (membrane
interactions break hydrogen bonds (e.g. proteins).
carbonate at high pH) Transporters allows the passage of hydrophobic solute by
LOWERINGthe energy of activation of the solute
CELL DOMAINS
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Transcribers: Aclan, J.V., Advento, V., Bolos, C.,Cabiscuelas, Y.N., Cuaderno, C., Gamboa, K.A., Javier, K., Laurilla, L.B., Rodenas, E., Roxas, F.
BIOCHEMISTRY Cell and Cell Membrane: A Biochemical Approach
examples
Transporters Channels + +
*Serotonin and Glutamate- K , *Monensin- Na channels
+ 2+
-Bind molecules and ions with high They show some specificity but Na , Ca *Gramicidin- folding creates
-
specificity, undergo conformational does not act like an enzyme and *Glycine- Cl Specific channels hollow channels
changes allowing the transport of only forms pores which open or
molecules and ions across close with much conformational +
*Dendrotoxin (mamba snake)- K *Diptheria toxin and activated
membranes changes
Biological
+
*Tetrodotoxin (puffer fish)- Na complement- create large
sources
- does not act like an enzyme, it *Cobrotoxin and alpha cellular pores causing lysis
-Catalyze transport at rates well conotoxin- Acetylcholine *Alpha-hemolysis (Strep.)- leak
is not saturable with ion
below the limits of free diffusion receptor ion channel out ATP
substrate (in contrast with
-saturable in the same sense as as
saturation kinetics seen in
enzymes so that futher increase in
transporters)
substrate conc. - Type of cell membrane transport that requires energy expenditure
-transport is FASTER
-does not provide a greater - Active transport is the diffusion of molecules and ions against its
THANtransporter which may
transport which SLOWER THAN electrochemical gradient with the use of energy which is mostly
reach the limit of unhindered
with channel supplied by ATP.
diffusion
o Its protein transporter has an ATPase activity hydrolyzing
Involve in passive (facilitated Mostly involve in facilitated ATP to ADP producing the needed energy.
diffusion) and active transport diffusion TYPES OF ACTIVE TRANSPORT
1. Primary Active Transport - solute accumulation coupled directly to
an exergonic chemical reaction such as breakdown of ATP
2. Secondary Active transport - occurs when endergonic (uphill)
Types of Transport Systems based on Direction of Movement
transport of one solute is coupled to an exergonic (downhill) flow of a
different solute that was originally pumped uphill by a primary active
transport.
Co-transport system- transfer of one solute depends upon the Figure 4.1. Illustrative concept of the types of active transport.
stoichiometric simultaneous or sequential transfer of another solute.
>>2 types
Symport- moves these solutes in the same direction
(eg Glucose – sodium transport)
Antiport-move two molecules in opposite directions
+ 2+
(eg, Na in and Ca out; Chloride-bicarbonate exchanger of the
RBC membrane)
Aquaporins
• water channels that only allow the passage of water molecules in
the membranes of RBC and cells of the collecting ductules of the
kidney.
• composed of tetramerictransmembrane proteins
• Mutation in some of these channel (AP-2) proteins may cause
nephrogenic Diabetes Insipidus
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Transcribers: Aclan, J.V., Advento, V., Bolos, C.,Cabiscuelas, Y.N., Cuaderno, C., Gamboa, K.A., Javier, K., Laurilla, L.B., Rodenas, E., Roxas, F.
BIOCHEMISTRY Cell and Cell Membrane: A Biochemical Approach
Figures 4.4 & 4.5 Some diseases associated with abnormalities in the cell membrane
and in ion channels. What is important to note here is the general concept that:
Genetic Mutations genes encoding for ion channels are therefore abnormal Ion
channel mutations abnormalities in ion transport diseases d/t channelopathies.
LIPOSOMES
Liposome-like structures underlie such things as LDL-particles and are
being used in medicine among other areas.
- Liposomes are bilayered lipid vesicles
Figure 4.3 Taken directly from the lecture slide; here are some types of ATP-driven - Form by sonicating lipids in aqueous solution
Active transporters. When ATP-driven is mentioned, it means that the channel
requires the use of Adenosine Triphosphate (ATP) as energy in order to establish the - Vehicles for drug, nucleic acid, Ab delivery
transport of the cellular material. - Used in cosmetics
- Liposomes can be filled with drugs, and used to deliver drugs for
NOTE: The discussion on Nerve Impulses involving ion channels and pumps is cancer and other diseases.
extensively discussed in Cell and Muscle Physiology; you may refer to your
Physiology trans or book for an easier concept.
****
Review Questions:
1. These interactions are the main driving force for the formation
of lipid bilayers.
a. Hydrophilic interactions
b. Hydrophobic interactions
c. Hydrogen bonding
d. Ionic bonding
2. Which of the following characterstics is shared by simple and
facilitated diffusion of glucose?
a. Occurs down an electrochemical gradient
b. Is saturable
c. Requires metabolic energy
d. Is inhibited by the presence of galactose
+
e. Requires a Na gradient
3. The following biochemical reactions occur in the cytoplasm,
EXCEPT:
a. Glycolysis
b. Glycogenesis
c. Kreb’s cycle
d. Amino acid synthesis
4. Prokaryotic cells, but not eukaryotic cells have:
a. Endoplasmic reticulum
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Transcribers: Aclan, J.V., Advento, V., Bolos, C.,Cabiscuelas, Y.N., Cuaderno, C., Gamboa, K.A., Javier, K., Laurilla, L.B., Rodenas, E., Roxas, F.
BIOCHEMISTRY Cell and Cell Membrane: A Biochemical Approach
b. Histones
c. Nucleoid
d. Nucleus
e. Plasma membrane
5. Mitochondria is associated with all of the following, EXCEPT:
a. ATP synthesis
b. DNA synthesis
c. Protein synthesis
d. Hydrolysis of various macromolecules at low pH
e. Two different membranes
6. Which of the following can transport a solute against its
concentration gradient?
a. Primary active transport
b. Facilitated transport
c. Simple diffusion
d. None of the above
7. According to the fluid mosaic model of a membrane:
a. Proteins are always completely embedded in the
lipid bilayer
b. Transverse movement (flip-flop) of a protein in the
membrane is thermodynamically favorable
c. The transmembrane domain has largely
hydrophobic amino acids
d. Proteins are distributed symmetrically in the
membrane
e. Peripheral proteins are attached to the membrane
only by noncovalent forces
8. The ion channel that is affected in cystic fibrosis.
a. Na+
+
b. K
c. Ca2+
d. Cl-
9. The most abundant type of phospholipid in cell membranes.
a. Sphingomyelin
b. Phosphoglycerides
c. Glycolipids
d. Cholesterol
10. Which of the following will specifically increase the fluidity of
the cell membrane?
a. Decrease in temperature
b. Increase the unsaturated fatty acids
c. Increase the saturated fatty acids
d. Removal of cholesterol
Answers
10.B
9.B
8.D
7.C
6.A
5.D
4.C
3.C
2.A
1.B
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Transcribers: Aclan, J.V., Advento, V., Bolos, C.,Cabiscuelas, Y.N., Cuaderno, C., Gamboa, K.A., Javier, K., Laurilla, L.B., Rodenas, E., Roxas, F.