Professional Documents
Culture Documents
2019
1A
1.01
BIOCHEMISTRY
LEARNING OBJECTIVES
1.
2.
3.
4.
4.
5.
6.
7.
8.
CELL MEMBRANE
Highly fluid, dynamic (exhibits rapid turnover and
lateral diffusion)
Asymmetric, sheet-like structures with inner and
outer surfaces
Viscous, plastic structures
o Ex. Red blood cells that have to pass
through sinusoid should be pliable.
Thermodynamically stable and metabolically
active
Noncovalent assemblies composed of lipids,
proteins and carbohydrates.
ASYMMETRY OF CELL MEMBRANE
INSIDE-OUTSIDE SYMMETRY
Irregular distribution of proteins
External location of carbohydrates
Specific enzymes exhibit specificity of location
Phospholipids (choline containing are external
while amino acid containing are in the inner leaflet)
REGIONAL ASSYMETRIES
Villous borders (i.e. villi found in the small
intestin, microvilli found in the ears and
fallopian tubes)
Gap junctions
Tight junctions
FUNCTIONAL PROPERTIES
1. Cell Individuality
2. Selective permeability (channels, transporters and
pumps)
3. Cell-cell interaction and adhesion
Page 1 of 13
BIOCHEMISTRY
Dr. Tengco | Cell and Cell Membrane
INTRACELLULAR
(High in)
+
K
2+
Mg
Proteins
Major anion: Phosphate
EXTRACELLULAR
(High in)
+
Na
2+
Ca
Glucose
Major Cation: Chloride
MEMBRANE LIPIDS
All major membrane lipids are amphipathic (have
both hydrophobic and hydrophilic regions)
Forms a lipid bilayer that is impermeable to watersoluble molecules.
Need for channels and transporters.
Lipid bilayers are formed by self-assembly driven
by hydrophobic effect
B. Sphingomyelin
Second major class of phospholipid
Sphingosine instead of glycerol is its
backbone
Ceramide = sphingosine + fatty acid
Hydroxyl group of sphingosine is esterified
to phosphorylcholine
Sphingomyelin is prominent in myelin
sheath
FATTY ACIDS
Saturated with straight tails (resulting to more rigid
cell membranes).
Unsaturated fatty acids have kinked tails (more
fluid membranes).
3 MAJOR MEMBRANE LIPIDS
1. PHOSPHOLIPIDS - lipids with phosphate groups.
A. Phosphoglycerides
Most common phospholipid
Consists of a glycerol backbone to which
are attached two fatty acids in ester
linkage and a phosphorylated alcohol like
ethanolamine, choline, serine, glycerol or
inositol.
Fatty acids are even-numbered (16-18 C
atoms) which could be saturated or
unsaturated.
Page 2 of 13
BIOCHEMISTRY
Dr. Tengco | Cell and Cell Membrane
MEMBRANE PROTEINS
The major functional molecules of membranes
Amphipathic: hydrophilic regions are protruding at
the inside and outside faces of the membrane but
connected by a hydrophobic region traversing the
hydrophobic core of the bilayer
Different membranes have varying protein
compositions
Functions of membrane proteins:
o Enzymes
o Pumps, channels, carriers
o Antigens
o Receptors
o Structural Proteins
Types of Membrane Proteins:
o Integral proteins:
Interact extensively with
phospholipids
Require detergents for
solubilization
Amphipathic, globular and, in
certain proteins, spans the
bilayerseveral times (eg, G
proteins)
Asymmetrically distributed in cell
membrane
The orientation was conferred by
the time of insertion to the bilayer
during synthesis in the ER
Most membrane proteins fall
under integral proteins
o Peripheral proteins
Do not interact directly with
phospholipids (do not require
detergents for release)
Weakly bound to hydrophilic
regions of integral proteins on one
side of the membrane
Ex: Ankyrin is bound to integral
protein Band 3; spectrin is in turn
bound to ankyrin (Figure 1).
MEMBRANE CARBOHYDRATES
Occur in association with lipids or proteins:
o Glycolipids
o Glycoproteins
Mostly found on the external membrane surface
Functions:
o Receptors
o
o
Antigens
Confers negative charge to cell (as
glycocalyx)
Page 3 of 13
BIOCHEMISTRY
Dr. Tengco | Cell and Cell Membrane
MEMBRANE FLUIDITY
critical to its function; some cells have acquired
the ability to vary the fluidity of their membranes
as needed
Factors that affect membrane fluidity:
1. Lipid composition
longer and more saturated fatty acid chains exhibit
higher transition temperature
Unsaturated fatty acids create a kink (bend)
Prevents fatty acids from packing together as
tightly
Decreases the melting temperature (increasing the
fluidity) of the membrane
2. Temperature
Transition Temperature (Tm) - temp at which
structure undergoes transition from ordered to
disordered state
* high temperatures = more fluid
* low temperatures = hydrophobic side chains
become aligned --> stiff structure
3. Cholesterol
moderator molecule
T above Tm, fluidity due to its rigid structure
(condensing effect)
T below Tm, fluidity (induces disorder)
Importance of Membrane Fluidity
Permeability to water and other hydrophilic
molecule increases
Lateral mobility of integral proteins increases*
o especially for transport and receptor
proteins
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BIOCHEMISTRY
Dr. Tengco | Cell and Cell Membrane
Uses:
o
o
o
GAP JUNCTIONS
Low resistance connections between the cells
Allow the movement of ions and small molecules
between the cells
Adjacent cells are coupled electrically
Connexon functional unit of gap junction
The alignment of a connexon of one cell with the
connexon of other cell forms a channel
Page 5 of 13
BIOCHEMISTRY
Dr. Tengco | Cell and Cell Membrane
LIPID RAFTS
Dynamic areas of the exoplasmic leaflet of the
lipid bilayer enriched in cholesterol, sphingolipids,
and proteins
Involved in and enhances signal transduction by
clustering the elements of signaling systems
PASSIVE TRANSPORT
Some molecules can passively traverse the bilayer
down electrochemical gradients by simple
diffusion or by facilitated diffusion
SIGNAL TRANSDUCTION
Signal transmission across the membranes
Biochemical signals from hormones,
neurotransmitters bind to receptors in cell
membrane
Through the generation of signaling moleculesm
the information is transmitted to the cytoplasm.
Signaling molecules:
o Cyclic nucleotides
o Calcium
o Diacylglycerol
o Phosphoinositides
TRANSPORT SYSTEM
Transfer of solutes and information across membranes.
Importance of transport systems:
Cell membrane is selective
Cell membrane receives and transmits signals to
and from other cells
Transport System according to Direction of Movement
1. UNIPORT
moves one type of substance bidirectionally (ie. Glucose transported into
cell through influence of insulin.)
2. COTRANSPORT
SYMPORT - moves two solutes in the
same direction (ie. Glucose transported
+
together with Na )
ANTIPORT - moves two solutes in
+
++
opposite directions (ie. Na (in) and Ca
+
or H (out) and Cl HCO3 exchanger in
RBC membrane)
Page 6 of 13
BIOCHEMISTRY
Dr. Tengco | Cell and Cell Membrane
Page 7 of 13
BIOCHEMISTRY
Dr. Tengco | Cell and Cell Membrane
FACILITATED DIFFUSION
a uniport system
explained by the PING PONG mechanism
o ping state = carrier is exposed to high
concentrations of solute. Molecules of the
solute bind to specific sites on the carrier
protein
o pong state = carrier is exposed to a lower
concentration of solute. Solute is
discharged (released from binding) where
it goes to the side of the membrane that
favors the new equilibrium
1.
2.
3.
4.
Page 8 of 13
BIOCHEMISTRY
Dr. Tengco | Cell and Cell Membrane
ACTIVE TRANSPORT
Transport is away from thermodynamic equilibrium (energy
requiring).
1. Primary active transport
Requires energy from light, electron movement
or ATP hydrolysis
energy for this process represents 30 40% of
energy expenditure of the cell
+ +
Ex: Na K ATPase
Is the transport of a solute across a membrane in
the direction of increasing concentration, and thus
requires energy (frequently derived from the
hydrolysis of ATP); a specific transporter (pump) is
involved
+
OSMOSIS
the net flow of solvent across a semipermeable
membrane from an area of LOWER SOLUTE
CONCENTRATION to an area of HIGHER
SOLUTE CONCENTRATION
due to a semipermeable membrane that only
allows the solvent to pass
affected by osmotic pressure
Page 9 of 13
BIOCHEMISTRY
Dr. Tengco | Cell and Cell Membrane
Osmotic Pressure
minimum pressure required to negate or reverse
osmosis.
force or pressure is applied on the side of the
membrane with higher solute concentration to
push the solvent back to the area with low solute
concentration
determined by the number of particles per unit
volume of fluid
volume may increase or decrease to
accommodate equilibrium if non-penetrating solute
is concerned
CELLULAR TRANSPORT OF MACROMOLECULES
involves vesicle formation with or from the plasma
membrane (PM)
Two process:
o endocytosis
o exocytosis
I. ENDOCYTOSIS
uptake of large molecules
o molecules taken up by the cell when
hydrolyzed yield nutrients
provides a mechanism for regulating the content of
certain membrane component (e.g. hormone
receptors)
responsible for DNA transfection (entry of DNA
into the cell)
o DNA from one cell transfecting a different
cell, altering the latters function and
phenotype
2+
2+
o uses Ca (Ca stimulates endocytosis
and precipitates DNA, making DNA a
better object for endocytosis)
involves macromolecules: proteins,
polysaccharides and polynucleotides
Requires the following:
o energy
2+
o Ca
o contractile elements/proteins
(microfilament system)
Types of endocytosis
1. PINOCYTOSIS
cellular uptake of fluid and fluid content
Two types of Pinocytosis:
a) Fluid-phase pinocytosis
also called cell drinking
is a nonselective process no
requirements
uptake of a solute thru small vesicle
formation that is proportionate to its
concentration in the ECF (extracellular
fluid)
is an active process (requires ATP)
b) Absorptive pinocytosis
is a receptor-mediated selective process
for the uptake of macromolecules
high affinity receptors permit the selective
concentration of ligands from the medium,
minimize the uptake of fluid or soluble
unbound macromolecules, and increase
the rate at which specific molecules enter
the cell
involves clathrin-coated pits
o cell membrane with
invaginations/pits where the
receptors for a particular molecule
can be found
o underneath the pits in the
cytosolic side is a contractile
protein called clathrin
may be a mechanism through which
certain viruses enter the cell causing
diseases
o HIV affects T cells
o Hepatitis liver cells
o Poliomyelitis motor neurons
e.g. LDL receptors cholesterol
Receptors that can recognize
carbohydrate moieties extracellular
glycoproteins
o Galactosyl receptors
asialoglycoproteins
o mannose 6-phosphate moiety
receptors acid hydrolases
Page 10 of 13
BIOCHEMISTRY
Dr. Tengco | Cell and Cell Membrane
ligand
receptor
pith
invagination
clathrin
A. Fluid-phase Pinocytosis
formation of invaginations which will become larger until
the two sides of the membrane fuse, sealing the neck of
the PM at the original site of invagination forming a fluidfilled vesicles
B. Absorptive Pinocytosis
formation of invaginations bringing the receptor inside it
for digestion (called internalization)
some receptors are digested like that of insulin receptor
(that is why people consuming too much sweets develop
Type II diabetes); some are returned back to the
membrane like that of LDL receptor
Fate of the vesicles after the invagination
acted upon by lysosomes producing primary
phagolysosomes that will eventually become secondary
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BIOCHEMISTRY
Dr. Tengco | Cell and Cell Membrane
II. EXOCYTOSIS
release of macromolecules to the exterior
(products coming from the cell going to the
outside)
from the site of production (ribosomes) that is
attached to the ER
transported to Golgi
apparatus for processing, packaging and
formation of vesicles
o when theres signal, vesicles will fuse with
the PM and extrude its contents outside
signal for initiation is often via a hormone binding
2+
to cell surface receptors
increasing Ca
2+
o Ca triggers exocytosis
Three fates of molecules released thru exocytosis:
1. attach to cell surface to become peripheral
proteins (e.g. antigen)
2. may become a part of extracellular matrix
(collagen, GAGs/glycosaminoglycans)
3. may enter ECF and signal other cells
(hormones and enzymes)
Page 12 of 13
BIOCHEMISTRY
Dr. Tengco | Cell and Cell Membrane
2 kinds of proteins :
those synthesized by membrane bound ribosomes
(secreted proteins and integral proteins) that
contain a SIGNAL PEPTIDE at their N-terminal
those synthesized by free ribosomes (cytosolic
proteins, extrinsic proteins in the inner Plasma
Membrane leaflet) that lack signal peptide
Page 13 of 13