Plasma Membrane FINAL

7/31/2019 Plasma Membrane FINAL

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Membranes: Their Structure,Function and Chemistry



The Functions of Membranes

1. Membranes define boundaries andserve as permeability barriers

a. Plasma(cell) membrane

b. Intracellular membranes

2. Membranes are sites of specific

functions

3. Membranes regulate the transport of

solutes

4. Membranes detect and transmitelectrical and chemical signals

5. Membranes mediate cell-to-cell

communication



Models of Membrane Structure

a) Lipid Nature of membrane

b) Lipid monolayer

c) Lipid bilayer

d) Lipid bilayer plus protein

lamellae

e) Unit membrane

f) Fluid-Mosaic model

g) Membrane protein structure

alpha helix

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Cell Membrane-separate the interior of the cell from its environment

-structure & function of cells are critically dependent on membranes

-formation of biological membranes is based on the properties of lipids

-all CMs share a common structural organization: bilayers of

phospholipids with associated proteins

-exhibits a fluid-mosaic model (by Singer and Nicholson)

-semi-permeable

Membrane Lipids

PHOSPHOLIPIDS -fundamental building blocks of all CM

-amphipathic molecules:

a) 2 hydrophobic fatty acidchains linked to a

b) phosphate contg hydrophilic head group- form bilayers in aqueous soln which forms

stable barrier

Plasma membrane- 50% lipid and 50% protein

Inner membrane of mitochondria- about 75% protein (reflecting the

abundance of protein complexes involved in electron

transport and oxidative phosphorylation)



Plasma membrane of E. coli- predominantly phosphatidylethanolamine

(80% of total lipid)

Mammalian PM- more complex contg 4 major phospholipids: phosphatidylcholine,

phosphatidylserine, phosphatidylethanolamine &

sphingomyelin(together constitute 50-60% of total membrane lipid)

- in addition to phospholipids, PMs of animal cells contain glycolipids &cholesterol

Plasma membrane

Lipid E. coli Erthrocyte Rough

endoplasmicreticulum

Outer

mitochondrialmembranes

Phosphatidylcholine 0 17 55 50

Phosphatidylserine 0 6 3 2

Phosphatidylethanolamine 80 16 16 23

Sphingomyelin 0 17 3 5

Glycolipids 0 2 0 0

Cholesterol 0 45 6 <5

Source: Data from P. L. Yeagle, 1993. The Membranes of Cells , 2nd ed. San Diego, CA: Academic Press.

a Membrane compositions are indicated as the mole percentages of major lipid constituents.

Table 2.3. Lipid Composition of Cell Membranes a

http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=cooper.glossary.2886









•Membranes function properly only in the fluid state

- T then fluidity; T then fluidity also

The effects of fatty acid composition on

membrane fluidity

- depends on the length of fa present and

degree of unsaturation of their side chainse.g. Membranes w/ Oleate (unsaturated

fa) are more fluid than stearate (saturated

fa)

The effects of sterols on membrane fluidity

-cholesterol has the paradoxical effect of

decreasing membrane fluidity at high T

and increasing at low T (in animal CMs)



Most organisms can regulate membrane fluidity

-whether prokaryote or eukaryote by 1oly changing

the lipid composition of the membranes

e.g poikilotherms (bacteria, fungi, protists, plants &

“cold-blooded” animals that can not regulate

their own temperature)

-membranes would gel upon cooling if they hadno way to compensate for the decrease in T

-at high T, their bilipid layers become so fluid that

they no longer serve as an effective permeability

barrier e.g. Cold-blooded animals (paralyzed by T >45oC)

possible reasons: nerve CMs become so leaky

to ions thus ion gradients can’t be maintained

and overall nervous function is disabled



e.g. homeotherm or “warm- blooded” organism-

effects on humans during chilly days, fingers and toes

get so cold that the membranes of sensory

nerve endings cease to function, resulting intemporary numbness

How to regulate or compensate T changes?

- by changing lipid composition of their membranes

thru Homeoviscous adaptation ( in poikilotherms)

-the main effect of this regulation is to keep

the viscosity of the membrane approximately

the same despite the changes in T

Example:1. Micrococcus (transferred from high T to

low T results to an increase in the

proportion of 16-C rather than 18-C fa

in the PM thus minimizing effect of thelow T.



*shorter fa chains decrease the melting T of a membrane

2. E. Coli (alteration in the extent of unsaturation of

membrane fa rather than in length)

-low T triggers synthesis of desaturase E that

introduces double bonds into the HC chains of fa.

- HVA also occurs in yeasts in plants (membrane fluidity

depend on the increased solubility of oxygen in the cyto-plasm at lower T)

Oxygen- substrate of desaturase E

Therefore: more Oxygen available at low T, more

unsaturated fa synthesized at rapid rate andmembrane fluidity increases

Amphibians and reptiles – adapt to lower T by increasing

proportion of unsaturated fa in their membrane as

well as cholesterol



Mammals or animals entering hibernation, the body T

drops substantially but adapts to this changeby incorporating a greater proportion of

unsaturated fa into membrane phospholipids

as its body T falls.



Membrane Proteins: The “Mosaic”

Part of the Model



MEMBRANE PROTEINS

-other major constituents of CM (25-75% of the massof the various membranes of the cell)

-carry out the specific functions of the different

membranes of the cell

some act as receptors that allow the cell to

respond to external signals

some are responsible for the selective transport

of molecules across the membrane

others participate in electron transport &

oxidative phosphorylationcontrol the interactions between cells of

multicellular organisms



-divided into 3 general classes:(based on the nature

of their attachment with the membrane)

a. integral membrane proteins- embedded

directly within the lipid bilayer(by the affinity of

hydrophobic segments on the protein for the

hydrophobic interior of the lipid bilayer)

b. peripheral membrane proteins- not inserted

into the lipid bilayer but are associated with the

membrane indirectly, generally by interactions with integral

proteins(hydrophilic, located on the surface of themembrane where they are linked noncovalently to the polar

head groups of

phospholipids and/or to the hydrophilic parts of other

membrane proteins)



c. Lipid-anchored proteins-though not a part

of the original fluid mosaic model but are

now included as a third class of membrane

lipids.-essentially hydrophilic proteins and reside

on membrane surfaces but they are

covalently bound to lipid molecules that are

embedded within bilayer



a. Integral monotopic proteins

- appear to be embedded on only one of the bilayer

b. Singlepass proteins

- transmembrane proteins that span the bilayer once

c. Multipass proteins

- span the bilayer multiple times

- may consist of either a1. single polypeptides

2. several associated polypeptides (Multisubunit

proteins)

d. Peripheral membrane proteins

- too hydrophilic to penetrate into the membrane

- attached to the membrane by electrostatic and H-bonds

that link them to adjacent membranes proteins or to

phospholipid headgroups



Lipid-anchored membrane proteins

-covalently bound to lipid molecules that are embedded

In the lipid bilayer 1. Fatty-acid or prenyl group – proteins on the inner

surface of the membrane

2. Glycosylphosphatidylinositol (GPI)

-most common lipid anchor -proteins on the outer membrane surface


http://slidepdf.com/reader/full/plasma-membrane-final 18/48Figure 2.48. Fluid mosaic model of membrane structure





Aquaporin

Transport Processes

Within a compositeEukaryotic cell



Important Transport Processes of the Erythrocyte

O i f M b T t P t i



Overview of Membrane Transport Proteins

Three Major classes of membrane transport proteins

1. ATP-powered pumps (simply pumps) – ATPases

that use the energy of ATP hydrolysis to move ions andsmall molecules across a membrane against a chemical

concentration gradient or electric potential

fxns: 1.maintain the low Ca+ and Na+ ion

concns inside all animal cells relative to

that in the medium2. generate the low pH inside animal-cell

lysosomes , plant-cell vacuoles and the

lumen of the stomach

2. Channel proteins – transport water or specifictypes of ions down their concn or electric potential gradients

- form a protein lined passageway

across the membrane through which multiple water

molecules or ions move simultaneously single file at every

rapid rate (up to 108 per second.)



-PM of all animal cells contains potassium-specific channel

proteins that are generally open and are critical to generating

the normal, resting electric potential across the PM

-other types of channel proteins are usually closed and openonly in response to specific signals.

3. Transporters- move a wide variety of ions and molecules

across CM- bind only one (or a few) substrate molecules

at a time

- after binding substrate molecules, the

transporter undergoes a conformational change

such that the bound substrate molecules (andonly these molecules) are transported across

the membrane.



3 types:

1. Uniporters –transport 1 molecule at a time

down a concn gradient

- moves glucose or amino acids

across the plasma membrane into

mammalian cells

2. Antiporters and symporters-couple the

movement of 1 type of ion or

molecule against its concn

gradient to the movement of adifferent ion or molecule down its

concn gradient.



-catalyze “uphill” movement of certain molecules(active transporters) but

unlike pumps, they do not hydrolyze ATP during transport.

-also known as cotransporters ( referring to their ability to transport two

different solutes simultaneously).

Figure 15-3. Schematic diagrams illustrating action of membrane transport proteins.





The Movement of Substances Across Cell Membranes

1. Passive Transport - does not require energy (eg. Simple diffusion, osmosis &

facilitated diffusion)- net movement of molecules & ions across a membrane

from higher to lower concentration (down aconcentration gradient)

2. Active Transport- requires expenditure of metabolic energy (ATP)

- involves carrier proteins- net movement across a membrane that occurs against

a concentration gradient (to the region of higher concentration)

*both leads to the net f lux of a particular ion or compound

NET FLUX – indicates that the movement of the substances into the cell(influx) and out of the cell (efflux) is not balanced, but

that one exceeds the other



2 Categories of Transport1. Non- carrier mediated –does not require carrier proteins(simple diffusion)2. Carrier-mediated –requires specific carrier proteins

a. facilitated diffusion (uniport)b. active transport

Fig. 4 Basic mechanisms by which solute molecules move across membranes



Diffusion- spontaneous process in which a substance moves from a region of

high concentration to a region of low concentration, eventually eliminating

the concentration difference between the two regions.- molecules that are non-polar (lipid –soluble) can easily pass thru

one side of the membrane to the other (eg. O2 or steroidhormones

- small molecules with polar covalent bonds but uncharged (eg. CO2,

ethanol ).Two Qualifications must be met before a nonelectrolyte can diffuse passively

across a membrane1. Substance must be present at high concentration on one side of themembrane than the other

2. Membrane must be permeable to the substance A membrane may be permeable to a given solute

1. bec that solute can pass directly thru the lipid bilayer2. bec that solute can traverse an aqueous pore that spans

the membrane and prevents the solute from coming into contact

with the lipid molecules of the bilayer





Examples

Factor More permeable Less Permeable Permeability

Ratio*1. Size: bilayer

more permeable

to smaller

molecules

H2O (water) H2N-CO-NH2

(urea)

102:1

2. Polarity: bilayer more permeable

to nonpolar

molecules

CH3-CH2-CH2-OH(Propanol)

HO-CH2-CHOH-CH2-OH (glycerol)

103:1

3. Ionic: bilayer

highlyimpermeable to

ions

O2 (oxygen) OH- (Hydroxide

ion)

109:1

*Ratio of diffusion rate for the permeable solute to the less permeable solute

Table 2. Factors Governing Diffusion Across Lipid Bilayers



THE DIFFUSION OF WATER THRU MEMBRANES-water molecules move much more rapidly thru a CM than do

dissolved ions or small polar organic solutes (CM is said to be semi-permeable)

OSMOSIS- the process where water moves readily thru a semi-permeablefrom a region of lower solute concn (↑ water concn) to a regionof higher solute concn (↓ water concn).

Two Requirements for Osmosis:

1. there must be a difference in the concn of a solute on the two

sides of a selectively permeable membrane2. the membrane must be relatively impermeable to the solute

*OSMOTICALLY ACTIVE – solutes that cannot freely passthru membrane



Osmotic pressure is defined as the hydrostatic pressure required tostop the net flow of water across a membrane separating solutions

of different compositions

Figure 5. Experimental system fordemonstrating osmotic pressure. Solutions A and B are separated by a

membrane that is permeable to water butimpermeable to all solutes. If C B (the totalconcentration of solutes in solution B) isgreater than C A , water will tend to flowacross the membrane from solution A tosolution B. The osmotic pressure p between

the solutions is the hydrostatic pressure that would have to be applied to solution B toprevent this water flow. From the van't Hoff equation, p=RT (C B−C A ).

http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mcb.glossdiv.7887

http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mcb.glossdiv.7887



Different Cells Have Various Mechanisms for Controlling Cell Volume

Figure 6-A. Response of animal cells to theosmotic strength of thesurrounding

Figure 6-B. The contractile vacuole inParamecium caudatum, a typical ciliated

protozoan, as revealed by Nomarskimicroscopy of a live organism.

Figure 6-C.Water relations in a plant cell.

PlasmolysisTurgidity



Water Channels Are Necessary for Bulk Flow of Water across Cell Membranes

AQUAPORINS- class of integral proteins that allow the passive movement of H2O from one side of the PM to the other- special water channels that allow water to move more

rapidly -in its functional form, aquaporin is a tetramer of identical

28-kDa subunits, each of which contains six transmembrane

α helices that form three pairs of homologs in an unusualorientation (Fig. 7A)-the channel through which water moves is thought to be lined

by eight transmembrane α helices, two from each subunit(Fig. 7B)

-Billions of water molecules-moving in single file- can pass

thru each channel every second

Osmosis- important factor in a multitude of bodily functions (eg. digestive tract

secretes several liters of fluid daily which is reabsorbed osmotically by the cellsthat line the intestine

Consequence: if fluid weren’t reabsorbed (in cases of extreme diarrhea) rapid dehydration occurs



-expressed in abundance in plant roots, erythrocytes and in other cells (e.g., the

kidney cells that resorb water from the urine) that exhibit high permeability for water.

•the hormone VASOPRESSIN (stimulates H2O retention by the collecting ductsof the kidney acts by way of these channels).-some cases of the inherited disorder CONGENITAL NEPHROGENICDIABETES INSIPIDUS have been traced to mutations in this aquaporinchannel. (persons suffering from this disease excrete huge quantities

of urine bec their kidneys do not respond to vasopressin)

Rate of Diffusion depends on:1. the magnitude of the concentration difference across the membrane

2. permeability of the membrane to the diffusing substances3. the temperature of the solution4. the surface area of the membrane thru which substances are diffusing

Ch l t i



Channel proteins

-facilitate diffusion by forming hydrophilic trans-

membrane channels

3 Kinds:

1. Ion channels

- transmembrane proteins that allow rapid

passage of specific ions (remarkably selective)

- single channel can conduct almost a million

ions per second!

-most ion channels are gated (opened and closed

by conformational changes in the protein regulating the

flow of ions thru the channel)3 gated channels:

1. Voltage-gated = open and close in response

to changes in membrane potential

2. Ligand-gated = triggered by the binding of s ecific substances to the channel rotein

3 M h iti d t



3. Mechanosensitive = respond to

mechanical forces that act on

membrane

2. Porins- transmembrane proteins that allow rapid passage

of various solutes

-pores found in the outer membranes of mitochondria,

chloroplasts and bacteria-larger & much less specific

-formed by multipass transmembrane proteins

-made of closed cylindrical ß sheet called ß barrel -inside pore (water-filled) is lined by polar chains while

outside that of nonpolar side chains-pore allows passage of various hydrophilic solutes

with size depending on the pore size of the particular

porin



3. Aquaporins (AQPs)

-transmembrane that allow rapid passage of water



Active Transport

-ATP-powered pumps that transport ions and

various small molecules against their concn

gradient



Three Major functions in cells and organelles:

It makes possible the uptake of essential nutrients

from the environment or surrounding fluid,even when the their concns in the environment

are much lower than inside the cell

it allows various substances (secretory prodts and

waste matls) to be removed from the cell or orga-

nelle, even when the concn outside is > than the

inside

it enables the cell to maintain constant, nonequi-librium intracellular concentrations of specific

inorganic ions such a K+, Na+, Ca+ and H+



2 types:

-based on the energy source

1. Direct active transport

-also called primary active transport -accumulation of solute molecules or ions on

one side of the membrane coupled directly

to an exergonic reaction particularly hydrolysis

of ATP.-transport proteins driven directly by ATP

hydrolysis are called ATPases or ATPase pumps.

2. Indirect active transport

-also called secondary active transport -depends on the cotransport of two solutes with

the movement of 1 solute down its gradient

driving the movement of the other solute up its

gradient.



Direct Active Transport Depends on Four Types of Transport

ATPases

-transport ATPases or pumps are responsible for mostdirect active transport in both prokaryotic and eukaryo-

tic cells.

1. P-type

2. V-type

3. F-type4. ABC-type



Table 2 1 Main Types of Transport ATPases (Pumps)



Solutes Transported Kind ofMembrane

Kind of Organisms Function of ATPase

P-type ATPases (P for

“phosphorylation”) Na+ and K+ Plasma

membrane

Animals Keeps [Na+] low and

[K+] high within cell;

maintains membrane

potential

H+ Plasma

membrane

Plants, fungi Pumps protons out of

cell; generatesmembrane potential

Ca2+ Plasma

membrane

Eukaryotes Pumps Ca2+ out of

cell;keeps [Ca2+] low

in cytosol

V-type ATPases (V for

“vesicle”

H+ Lysosomes;secre-

tory vesicles

Animals Keep pH in organelle

low, which activates

hydrolytic enzymes

H+ Vacuolar

membrane

Plants, fungi Keeps pH in vacuole

low,which activates E

Table 2.1 Main Types of Transport ATPases (Pumps)

F Type ATPases (F for



F-Type ATPases (F for“factor”); also called

ATP synthases

H+ Inner mitochondrial

membrane

Eukaryotes Generates H+ gradient

that drives ATP synthesis

H+ Thylakoid membrane Plants Generates H+ gradientthat drives ATP synthesis

H+ Plasma membrane Prokaryotes Generates H+ gradient

that drives ATP synthesis

ABC ATPases (ABC for“ATP-binding

cassette”)

A variety of solutes* Plasma membrane,

Organellar membranes

Prokaryotes, eukaryotes Nutrient uptake; protein

export; possibly also

transport into and out of

organelles

Antitumor drugs** Plasma membrane Animal tumor cells Removes hydrophobic

drugs(and hydrophobic

natural prodts from cell)

*Solutes include ions, sugars, amino acids, carbohydrates, peptides and proteins**Drugs include colchicine, taxol, vinblastine, actinomycin D, and puromycine

Na+/K+ ATPase maintains the Intracellular Na+ & K+ concns in Animal Cells



Figure 15-13. Models for the structure andfunction of the Na+/K+ ATPase in the plasmamembrane. (a) This P-class pump comprises

two copies each of a small glycosylated β

subunit and a large α subunit, which performsion transport. Hydrolysis of one molecule of

ATP to ADP and Pi is coupled to export of

three Na+ ions (blue circles) and import of two

K+ ions (dark red triangles) against their

concentration gradients (large triangles). It is

not known whether only one α subunit, or both,in a single ATPase molecule transports ions.

(b) Ion pumping by the Na+/K+ ATPase

involves a high-energy acyl phosphate

intermediate (E1~P) and conformational

changes, similar to transport by the muscle

Ca2+ ATPase. In this case, hydrolysis of the

E2 –P intermediate powers transport of asecond ion (K+) inward. Na+ ions are indicated

by blue circles; K+ ions, by red triangles. See

text for details. [Adapted from P. Läuger, 1991,

Electrogenic Ion Pumps, Sinauer Associates,

p. 178.]

Indirect Active Transport: Sodium Symport Drives the Uptake of Glucose



Indirect Active Transport: Sodium Symport Drives the Uptake of Glucose

Figure 15-19. Proposed model for operation of the two-Na+/one-glucose symporter. The simultaneous binding of Na+ and glucose to sites

on the exoplasmic surface induces a conformational change, generating atransmembrane pore or tunnel that allows both bound Na+ and glucose to

move through the protein to binding sites on the cytosolic domain and then

to pass into the cytosol. After this passage, the protein reverts to its original

conformation. [See E. Wright, K. Hager, and E. Turk, 1992, Curr. Opin. Cell Biol. 4:696 for details on the structure and function of this and related

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Plasma Membrane FINAL