CH 40 part 1 & 2

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1. Membranes Highly fluid, dynamic structures with lipid 11. Major lipids Phospholipids, Glycosphingolipids snd
bilayer and associated CHON Cholesterol
2. Plasma - define cell boundaries 12. 1. Phosphoglyceride - more common
membrane - Exchanges materials wit EC by exocytosis and Backbone: glycerol phosphate; 2 FA
endocytosis and ROH attached to it via ester
- Key role in cell-cell interaxn, transmembrane linkages
signaling Fatty acids: even numbered C mol (16
- has Selective permeability & acts as barrier or 18), unbranched and can be
thereby maintaining differences in and out of unsaturated or saturated with one or
cell more double bonds
- selective membrane molecular permeability is Alcohol: choline, ethanolamine,
generated through action of specific glycerol, inositol, serine
TRANSPORTERS and ION CHANNELS
13. Phosphatidylcholine major phosphoglyceride by mass in
3. IC -Form specialized compartments within cell human
Membranes - shapes organelles
14. Phosphatidic acid Simplest phosphoglyceride
- Localize enzymes
- function as integral elements elements in 15. 2. Sphingomyelin Backbone: sphingosine; FA is attached
excitation-response coupling to N group by amide linkage ->
- provide sites of energy transduction such as ceramide + primary hydroxyl group is
photosynthesis (chloroplasts), oxidative esterified to phosphorylcholine
phosphorylation (mitochondria) - Prominent in myelin sheaths
- structures and surfaces are protein studded, 16. Glycosphingolipid Backbone: ceramide
sheet like, non covalent assemblies that form Sugar containing lipids
spontaneously in water d/t amphiphatic nature - galactosyl and glucosyl ceramides
of lipids & CHON contained within the (cerebrosides) and gangliosides
membrane - loc in plasma membrane and sugar
4. Changes in can affect water balance & ion flux component is outside of cell
membrane 17. Sterols - Most common sterol in the
5. Gap Where adjacent cells may exchange material membranes of animal cell is
junction CHOLESTEROL
- Reside within plasma membrane
6. Normal cell Depend on Normal membrane
- intercalates among phospholipids
fxn
- hydrophilic OH group at aqueous
7. H2O 60% of lean body mass interface and remainder of mol. is
buried within lipid bilayer leaflet
8. ICF - 2/3 of TBW, provides specialized
- CHOLESTEROL not present in plants
compartment for cell to:
(1) make, store and utilize energy 18. Lipid separation Can be done by column, tlc, gas liquid
(2) repair itself chromatography
(3) replicate
19. Membrane lipids Contains:
(4) perform cell-specific fxn
are amphipathic Hydrophobic region: insoluble in h2O,
Cation: Na, CA
soluble in organic solvents
Major Anion: Cl
Hydrophilic region: soluble in h2o
9. ECF - 1/3 of TBW
- distributed between PLASMA and IF Saturated FAs form relatively steaight
- is a delivery system, brings to the cells tails
nutrients, o2, ions, minerals and hormones Unsaturated FAs form "kinked" tails
- removes co2, waste products and toxic or -> INC double bonds = INC kinked
detoxified materials tails = Membrane become less tightly
Cations: K, Mg packed and more fluid
Major anion: phosphate
20. Detergents Solubilize and purify membrane
10. Cystosol Contains high conc. Of CHON that acts as CHON
major intracellular buffer
21. Membrane If solvent is H2O: phospholipids spontaneously 30. Diff Membranes are dynamic structures
lipids form organize themselves into MICELLES membranes -Membrane lipids and CHON undergo
Bilayer & comp turnover
- Proteins - major fxnal molecules of
22. Bilayers - Hydrophobic regions of phospholipids are
membranes, consist of enzymes, pumps and
exits as sequestered from aqueous environment
transporter channels, Ags and receptors
sheets - hydrophobic, charged portions are exposed
- Nonmobile CHON do not exhibit lateral
to water
(faster) diffusion because they are anchored
- impermeable to most water soluble
to underlying actin cytoskeleton
molecules
- Transverse movements of lipids across
- self assembly of lipid bilayers is driven by
membrane (flip flop) is extremely slow
hydrophobic effect
- INC entropy - d/t release of effect 31. Membranes Inside-outside asymmetry: outside surface
immobilized H2o are differs from inside; CHON CHO
asymmetric
23. Lipid - Readily enters cell
Choline containing phospholipids -
soluble - o2, co2, nitrogen, indole
phosphatidylcholine and sphingomyelin are
- permeability coefficient of small mols in lipid
located mainly in the outer leaflet
bilayer correlate with their solubilities in
nonpolar solvents
Aminophospholipids - phospatidylserine
- many drugs are hydrophobic and can readily
and phosphatidylethanolamine are
cross membrane
preferentially located in inner leaflet
24. Non Lipid - Membranes contain CHON, many span lipid
Soluble bilayer - there must be limited transverse mobility
-form channels for movement of ions and (flip-flop) of the membrane phospholipids
small mols serve as transporters (t1/2 = weeks)
25. Membrane - Membrane phospholipids act as solvent for 32. *Translocases transfer phospholipid from inner to outer
CHON in membrane CHON (Flippases) leaflet
bilayer - a-helical structure of CHON minimizes the
33. how lipids (1) transport from the ER in vesicles, which
hydrophilic character of peptide bonds;
enter then transfer the contained lipids to the
CHON can be amphipathic
membranes recipient membrane;
- a stretch of ~ 20 AA in an a-helical will span
(2) entry via direct contact of one membrane
the lipid bilayer
(eg, the ER) with another, facilitated by
26. Hydropathy Calculate whether a particular sequence of specific proteins;
plot amino acids is consistent with transmembrane (3) transport via the phospholipid exchange
location proteins (also known as lipid transfer
27. Protein - Some CHON anchored to one leaflet of proteins), which only exchanges lipids, but
lipidation bilayer to certain lipids does not cause net transfer.
- can occur at protein termini (N- or C-) or 34. Further with regard to glycosphingolipids and
internally asymmetry glycoproteins; the sugar moieties of these
- can only occur on specific subset of CHONs molecules all protrude outward from the
28. C terminal Isoprenylation, Cholesterylation, plasma membrane and are absent from its
Glycophosphatidylinositol inner face

29. N Terminal Myristoylation, internal cysteine S-prenylation, 35. Integral - most membrane CHONs, interact
S-acetylation CHON extensively with phospholipids
- require use of detergents for solubilization
- generally span the bilayer as a bundle of a-
helical transmembrane segments
- usually globular and amphipathic
- asymmetrically distributed across the
membrane bilayer
36. Peripheral - do not interact directly with the hydrophobic 42. Cholesterol - acts as a buffer to modify the fluidity of
CHON cores of the phospholipids in the bilayer membranes.
- do not require use of detergents for their - At temperatures BELOW the Tm, it interferes
release. with the interaction of the hydrocarbon tails of
- bound to the hydrophilic regions of specific fatty acids and thus increases fluidity.
integral proteins and head groups of - At temperatures ABOVE the Tm, it limits
phospholipids and can be released from them disorder because it is more rigid than the
by tx with salt solutions of high ionic strength. hydrocarbon tails of the fatty acids and cannot
e.g ankyrin & spectrin - maintain biconcave move in the membrane to the same extent,
shape of RBC thus limiting fluidity.
- At high cholesterol phospholipid ratios,
37. Artificiial - consist of mixtures of one or more
transition temperatures are altogether
membranes phospholipids of natural or synthetic origin
indistinguishable.
that have been treated by using mild
sonication to induce the formation of spherical 43. fluidity of a signicantly affects its function:
vesicles in which the lipids form a bilayer. membrane - As membrane fluidity increases, so does its
permeability to water and other small
38. liposomes lipid bilayer with an aqueous interior
hydrophilic molecules.
39. uses of 1. The lipid content of the membranes can be - Lateral mobility of integral proteins increases
artificial varied as the fluidity of the membrane increases.
membrane 2. proteins or enzymes can be incorporated
44. insulin - example of altered function with changes in
systems into these vesicles
receptor fluidity
3. environment can be controlled and varied
- As the concentration of unsaturated fatty
4. entrap compounds (Drugs, isolated genes)
acids in the membrane is increased (by
40. Fluid 1972 - singer and nicholson growing cultured cells in a medium rich in such
mosaic - The phase changes — fluidity of membranes mols), fluidity increases -> alters receptors and
model — are largely dependent upon the lipid binds more insulin
composition of the membrane -> At normal body temp (37°C), the lipid
- As TEMP INC: the hydrophobic side chains bilayer is in a fluid state.
undergo a transition from the ordered state
45. Lipid rafts - specialized areas of the exoplasmic (outer)
(more gel-like or crystalline phase) to a
leaflet of the lipid bilayer enriched in
disordered one, taking on a more liquid-like or
cholesterol, sphingolipids, and certain proteins
fluid arrangement.
- hypothesized to be involved in signal
41. transition - The temperature at which membrane transduction and other processes.
temperature structure undergoes the transition from - clustering certain components of signaling
ordered to disordered (ie, melts) systems closely together may increase the
- Longer and more saturated fatty acid chains efficiency of their function.
interact more strongly with each other via
46. Caveolae - may derive from lipid rafts.
their extended hydrocarbon chains and thus
- flask-shaped indentations of the cell
cause higher values of Tm—that is, higher
membrane into the cytosol
temperatures are required to increase the
- many, if not all, contain the protein caveolin-1
fluidity of the bilayer.
- Proteins detected in caveolae include various
- Unsaturated bonds that exist in the cis
components of the signal transduction system
configuration tend to increase the fluidity of a
(eg, the insulin receptor and some G proteins),
bilayer by decreasing the compactness of the
the folate receptor, and endothelial nitric
side chain packing without diminishing
oxide synthase (eNOS).
hydrophobicity
47. Tight - often located below the apical surfaces of
junctions epithelial cells
- prevent the diffusion of macromolecules
between cells.
- composed of various proteins, including
occludin, various claudins, and junctional
adhesion molecules.
48. other found in the surface membranes are: 55. Hormones - can regulate facilitated diffusion by
special Desmosomes, Adherens junctions, and changing
structures Microvilli the number of transporters available.
49. Passive - down electrochemical gradients 56. Insulin - Via a complex signaling pathway increases
diffusion - spontaneous movement toward equilibrium glucose transport in fat and muscle by
- simple or facilitated; see table 40-3 recruiting glucose transporters (GLUT) from
an intracellular reservoir.
50. Simple - passive flow of a solute from a higher to a
-also enhances amino acid transport in liver
diffusion lower conc. due
and other tissues.
to random thermal movement.
- Limited by 3 factors: 57. Glucocorticoid Enhance transport of amino acids into liver,
(1) the thermal agitation of that specific where the amino acids then serve as a
molecule; substrate for gluconeogenesis.
(2) the concentration gradient across the
58. Growth increases amino acid transport in all cells,
membrane
hormone and estrogens do this in the uterus.
(3) the solubility of that solute
59. Ion Channels - Are Transmembrane Proteins That Allow
51. Factors (1) concentration gradient across the
the Selective Entry
affecting membrane—solutes move from high to low
of Various Ions
net conc
- porelike structures composed of proteins
diffusion (2) electrical potential across the membrane:
- very selective, activity can be regulated
solutes move toward the solution that has the
- are open transiently and thus are "gated."
opposite charge. Inside of cell (-) charge
Gates can be controlled by opening or
(3) permeability coefficient of the substance
closing. (ligand, voltage, mechanical)
for the membrane;
- In ligand gated channels, a specific
(4) hydrostatic pressure gradient across the
molecule binds to a receptor and opens the
membrane: increased pressure will increase the
channel.
rate and force of the collision between the
- Voltage-gated channels open (or close) in
molecules and the membrane;
response to changes in membrane
(5) temperature, increased temperature will
potential.
increase particle motion and thus increase the
- Mechanically gated channels respond to
frequency of collisions between external
mechanical stimuli(pressure and touch).
particles and the membrane.
60. permeability depend on:
52. Facilitated - involves either certain transporters or ion
Size, Extent of hydration & extent of charge
diffusion channels
density of ion
- is passive transport of a solute from a higher
to a lower concentration mediated by a specific 61. features of ion (1) their overall structures;
protein transporter. channels that (2) how they conduct ions so rapidly;
must be (3) their selectivity;
53. ping-pong in this model, the carrier protein exists in two
elucidated: (4) their gating properties.
mechanism principal conformations.
"ping" state - it is exposed to high 62. Transporters - Are Specific Proteins Involved in
concentrations of solute, and molecules of the Facilitated Diffusion & Also Active Transport
solute bind to specific sites on the carrier 63. Uniport moves one type of molecule bidirectionally.
protein. Binding induces a conformational system
change that exposes the carrier to a lower
64. cotransport transfer of one solute depends upon the
concentration of solute ("pong" state).
systems stoichiometric simultaneous or sequential
- process is completely reversible, and net flux
transfer of another solute.
across the membrane depends upon the
concentration gradient. 65. symport moves two solutes in the same direction.
54. determines (1) the concentration gradient across the 66. Antiport move two molecules in opposite directions
rate at w/c membrane; systems (eg, Na+ in and Ca2+ out)
solutes (2) the amount of carrier available (this is a key
enter cell control step);
via FD (3) the affinity of the solute-carrier interaction;
(4) the rapidity of the conformational change
for both the loaded and the unloaded carrier
67. similarities between passive and active transports & 74. Aquaporins Are Proteins That Form Water Channels in
substrate-enzyme interaxn: Certain Membranes
1. there is a specific binding site for the - tetrameric transmembrane proteins
solute - in red cells ad cells of collecting
2. there carrier is saturable, so it has a max. ductules of the kidney
rate of transport (vmax) - oxygen atom of water binds to two
3. there is a binding constant (km) for the asparagine residues lining the channel,
solute and the whole system has km making the water unavailable to participate
4. structurally similar competitive inh. block in an H+ relay, and thus preventing entry of
transport protons.
*transporters are like enzymes but generally - Mutations in the gene encoding AP-2
do not modify their substrates have been shown to be the cause of one
type of nephrogenic diabetes insipidus, a
68. cotransporters - use gradient of one substrate created by
condition in which there is an inability to
active transport to drive the movement of
concentrate urine.
the other substrate
- The Na+ gradient produced by the Na+-K+- 75. Active Differs from diffusion in that molecules are
ATPase is used to drive the transport of a transport transported against concentration
number of important metabolites. gradients
- ATPase: very important example of
76. Maintenance of Consumes approx 30% of total energy
primary transport
electrochemical expenditure in a cell
- Na+-dependent systems: example of
gradient
secondary transport that rely on the
gradient produced by another system 77. Four major P, F, V and ABC transporters
- Thus, inhibition of the Na+ K+-ATPase in classes of ATP-
cells also blocks the Na+-dependent uptake driven active
of substances like glucose. transporters

69. Ionophores Are Molecules That Act as 78. P class Na-K-ATPase pump; Ca2+ ATPase (SR)
Membrane Shuttles for Various Ions 79. F type mt ATP synthase is most important
- small cylic organic molecules that certain example; oxidative phosphorylation
microbes synthesize
80. V type Pump proteins into lysosomes and other
- contain hydrophilic centers that are
structures
surrounded by peripheral hydrophobic
regions. 81. ABC Include CFTR protein, a chloride channel
- Specific ions bind within the hydrophilic transporters involved in the causation of cystic fibrosis.
center of the molecule, which then diffuses
through the membrane efficiently delivering Another example is multidrug resistance-1
the ion in question to the cytosol. protein (MDR-1 protein)
70. valinomycin function as shuttles for the movement of 82. Na-K-ATPase Key enzyme in regulating intracellular
ions (K+) concentration if Na and K
71. gramicidin fold up to form hollow channels through
Pumps 3 Na out and 2 K into cells
which ions can traverse the membrane.
72. microbial such as diphtheria toxin and activated serum Integral membrane protein that contains a
toxins complement components - can produce transmembrane domain allowing passage
large pores in cellular membranes and of ions, and cytosolic domains that couple
thereby provide macromolecules with direct ATP hydrolisis to transport
access to the internal milieu.
83. Electrogenic Differential ion transport creates a charge
73. a-hemolysin - produced by certain species of effect imbalance between the inside and the
toxin Streptococcus) consists of seven subunits outside of the cell, making the cell interior
that come together to form a β-barrel that more negative.
allows metabolites like ATP to leak out of
84. Ouabain and Cardiac drugs that Inhibit the Na-K-ATPase
cells, resulting in cell lysis.
digitalis by binding to the extracellular domain
85. Membrane Maintain asymmetry of inside-outside 100. Secondary Contain hydrolytic enzymes.
enclosing voltage(electrical potential) and is also lysosomes Specialized organelles for intracellular
neuronal electrically excitable due to the presence of disposal
cells voltage gated channels
101. Endocytosis 1. Energy (from hydrolysis of ATP)
86. Myelin Formed by Schwann cells. requirements 2. Ca2+
sheets 3. Contractile elements in the cell
Wrap around nerve fibers and provide an (microfilament system)
electrical insulator that surrounds most of the
102. 2 types of Phagocytosis and Pinocytosis
nerve and greatly speeds up propagation of
endocytosis
the wave (signal) by allowing ions to flow in
and out of the membrane 103. Phagocytosis Occurs in specialised cells
"eating" (macrophages and granulocytes)
87. Nodes of Region of the membrane where the membrane
Ranvier is free of insulation
Ingestion of large particles (viruses,
88. Multiple Dse characteriEd by demyelination and bact, cells or debris)
sclerosis impaired nerve conduction
and
Guillain- Not all cells
Barré
104. Macrophages Extremely active. May ingest 25% of
syndrome
their volume per hour; internalize 3%
89. 1st step in Entry of glucose into the cells of its plasma membrane each minute
energy or the entire membrane every 30 mins
utilization
105. Pinocytosis Property of all cells. Leads to cellular
90. GLUT 4 Transport system In adipocytes and skeletal "drinking" uptake of fluid and fluid contents.
muscles; enhanced by insulin
106. Fluid-phase Non-selective process. Solute uptake
91. Na-glucose Located at the apical surface; binding site of pinocytosis by formation of small vesicles
symporter glucose and Na proportionate to its concentration in
the surrounding ECF.

Na drags glucose. Extremely active. Example: fibroblasts.

92. Transport Involves a uniport that allows glucose 107. Absorptive Uptake of specific macromolecules
movement accumulated within the cell to move across the pinocytosis or for which there are binding sites in the
of glucose basolateral membrane; involves GLUT2 receptor mediated plasma membrane.
endocytosis
93. Cholera Treated with oral rehydration therapy,
consisting primarily of NaCl and glucose.
Vesicles formed are derived from
Glucose and sodium transport across the
invaginations (pits) that are coated on
intestinal epithelium via osmosis results in
the cytoplasmic side with a
rehydration
filamentous material
94. Endocytosis Process by which cells take up large molecules
108. Coated pits Invaginations (pits) coating the
95. DNA Depends upon endocytosis, which is cytoplasmic side with a filamentous
transfection responsible for entry of DNA into the cell; material. Constitute 2% of the cell
exps commonly use calcium phosphate surface of some cells.
96. Calcium Stimulates endocytosis and precipitates DNA, 109. Clathrin Protein in many systems that is the
which makes DNA a better object for filamentous material; has 3 limbed
endocytosis. structure (triskelion with 1 light and 1
97. Exocytosis Macromolecule release by cells heavy chain)

98. exocytosis Both involve vesicle formation with or from 110. Assembly particles Direct the polymerization of clathrin
and plasma membrane into a vesicle. Composed of 4 adapter
endocytosis proteins.

99. Primary fuse with endocytic vesicles to form secondary 111. Phosphatidyinositol Important role in vesicle assembly.
lysosomes lysosomes 4,5 - bisphosphate
(PIP2)
112. Dynamin Both binds and hydrolyzes GTP. 123. Transmembrane Process by which specific biochemical
signalling signals such as neurotransmitter,
Necessary for the pinching off of clathrin- hormones, and immunoglobulins bind to
coated vesicles from the cell surface. integral transmembrane receptor proteins
via their exposed extracellular domains,
113. LDL molecule Internalized by means of coated pits
resulting to transmission of information to
and receptor containing LDL receptor.
the cytoplasm.
Endocytic vesicles containing LDL- bound
LDL receptor complex fuse to lysosomes in
Involves the generation of a number of
cells.
second messenger signalling molecules
114. LDL receptor Regulated by secondary or tertiary (cyclic nucleotides, calcium,
consequences of pinocytosis. Ex.: metabolic phosphoinositides and diacylglycerol.
products such as chole released during the
124. Gap junctions Structures that permit direct transfer of
degradation of LDL.
small molecules (up to ~1200 Da) from one
115. Extracellular Requires that the glycoproteins carry cell to its neighbour.
glycoproteins specific carbohydrate recognition signals.
125. Connexins Composes the gap junctions forming a
116. Galactosyl Loc on the surface of hepatocytes, is bihexagonal structure consisting of 12
receptor instrumental in the absorptive pinocytosis of such proteins.
asialglycoproteins from the circulation.
117. Acid Taken up by absorptive pinocytosis in 6 conexins form a connexion hemichannel
hydrolases fibroblasts are recognized by their and join to a similar structure in a
mannose-6-phosphate moieties. neighboring cell to make a complete
connexion channel.
118. Mannose 6- Plays in important role in intracellular
phosphate targeting of the acid hydrolases to the 126. Diseases assoc Cardiovascular abnormalities.
moiety lysosomes of the cells in which they are with genes One type of deafness.
synthesized coding for X-linked form of Charcot-Marie-Tooth
connexions disease (a demylenating neurologic
disorder.
Viruses (poliomyelitis, hepa and AIDS) 127. Extracellular New, important mediator of cell-cell
initiate their infectious cycle thru the above vesicles communication that likely contribute
mechanism. (EXOSOMES) importantly to both normal and
119. Iron toxicity Begins with excessive uptake due to pathological physiology.
endocytosis
Eclosed by a lipid bilayer. Heterogenous
120. Exocytosis Most cells release macromolecules to the
in size (30-2000nm diameter)
exterior thru this process.
128. 2 mechanisms 1. Budding from the plasma membrane of
121. "Classical Signal is a hormone which, when it binds to a
that generate a source cell - Microvesicles
exocytosis" cell-surface receptor, induces a local and
extracellular 2. Generated from multivesicular
transient change in Ca conc. Ca triggers
vesicles body(MVB), a component of the
exocytosis.
endocytic membrane transmembrane
122. 3 fates of 1. They are membrane proteins and remain trafficking system. - Exosomes
molecules associated with the cell surface
released by 2. They can become part of the extracellular **both ultimately fuse to their target cell
exocytosis matrix. Ex. Collagen and to deliver a distinct "payload." Often these
glycosaminoglycans terms are collectively known as
3. They can enter the ECF and signal other "exosomes."
cells.
129. Exosomes Secreted from the source cell upon fusion
*insulin, PTH, and catecholamines are all
of the MVB and plasma membrane.
packaged in granules and processed within
cells, to be released upon appropriate 130. Proteins in Receptors, transporters, ion channels,
stimulation. plasma enzymes and structural components.
membranes are
classified as:
131. Receptor mutations Cause defects in transmembrane signalling(common in cancer)
132. Mutations in genes encoding Cause neurologic and other problems (ex. Leber hereditary optic neuropathy [LHON]).
mitochondrial membrane proteins
involved in oxidative
phosphorylation
133. Myasthenia gravis Caused by formation of autoantibodies to acetylcholine receptor in skeletal muscles
134. Multidrug resistance Caused by overexpression of P-glycoprotein (MDR-1), a drug pump.
135. Excess cholesterol(membrane Familial cholesterolemia
constituent Abn)
136. Lysophospholipids(membrane After bites by certain snakes, whose venom contains phospholipases
constituent Abn)
137. Cystic Fibrosis A recessive genetic disorder prevalent among whites in North America and certain parts of
Northern Europe.

Characterized by chronic bacterial infections of the airways and sinuses, fat, maldigestion
due to pancreatic exocrine insufficiency, infertility in males due to abnormal development of
the vas deferens, and elevated levels of chloride in sweat (>60mmol/L)

Mutation in Cystic Fibrosis Transmembrane Regulatory Protein (CFTR).

138. CFTR Cyclic AMP-regulated Cl transporter.