Horton Moran Scrimgeour Perry Rawn

Principles of Biochemistry Fourth Edition

Chapter 9
Lipids and Membranes

Copyright 2006 Pearson Prentice Hall, Inc.

Lipids
Storageenergy:triacylglycerol(fat,oil)
Cellmembrane:glycerophospholipids,sphingolipids,sterols
Protectivesurface:wax(incellwall,exoskeleton,skin)
Enzymecofactor:
Electroncarrier:cytochromeP450
Lightabsorbingpigments:chlorophyll
Hydrphobicanchors
Emulsifyingagents
Hormones:testosterone,estradiol
Interacellularmessengers:sialicacid

Structural relationships of the major classes of lipids

p. 254

Fattyacid

Saturated
fatty acid

Unsaturated
fatty acid

IUPC:InternationalUnionofPureandAppliedChemistry
p. 255

Structure and nomenclature of fatty acids

Fattyacid:

Fuel:
~37kJ/gfattyacid
~16kJ/gproteinorcabohydrate
pKa4.5~5.0,ionizedatphysiological
pH
Asadetergent,withpolarheadand
hydrophobictail
Lowconcentrationinmembrane
Joinedtoothermolecularwithester
linkage

: tail, farthest from the

carboxyl carbon
-3, e.g. 18:3 9,12,15
-6, e.g. 18:2 9,12
-9, e.g. 18:1 9
p. 256

Chemical structures of three C18 fatty acids

p. 257

Triacylglycerol

Structure of glycerol and triacylglycerol

Pancreatic
lipases

Fat(solid)andoil(liquid)are
mixtureoftricaylglycerols.
Mostdietlipids:tricaylglycerols.
Mostabundantlipidinanimal.
Notfoundincellmembrane.
Pancreaticlipaseshydrolysethe
ester(atC1andC3)of
gtracylglycerol.
p. 258

Glycerolphospholipids

Glycerolphospholipids
Mostabundantincell
membrane
Contain:
Glycerolbackboned
2acylgroupsatC1,C2
PhosphateatC3

Named:PhosphatidylX
p. 260

p. 261

Action of four phospholipases

Disruptcellmembrane.
Presentinpancreaticjuice,
snake,bee,andwaspvenom.
p. 261

Structure of an
ethanolamine
plasmalogen

Ethanolamine

Ethanolamineandcolinearethe
commonlyesterifiedto
plasmalogen.
About23%oftheglycerophospho
lipidinthehumancentralnerve
system,alsofoundinthemembrane
ofperipheralnerveandmuscle.

p. 262

Sphingolipids

Structures of sphingosine, ceramide, and sphingomyelin.

p. 262

Structure of a galactocerebroside

Galactocerebrosides are
abundant in nerve tissue, about
15% lipid of myelin sheaths.

p. 263

Ganglioside GM2

GM2isthe2ndmonosialoganglioside
caracterized.
Now>60gangliosides.
Gangliosides:ceramide+C1Glc+Gla
Presentoncellsurface
p. 263

Inheritedhumandiseases
resultingfromabnormal
accumulationof
membranelipids.
Pathwayforthebreakdown
ofGM1,globosideand
sphigomyelin.
GM2Lysosomesswell
nervecellsenlargement
nervecellsdie
blindness,mental
retardation,death

Lehninger,p356

ABO Blood Group

Lehninger,p354

ABO blood group is determined by a single gene on chromosome 9.

Single deletion at N-terminal: non-functional O allele
A enzyme: N-acetylaminogalactosyltrnasferase
B enzyme: galactosyltrnasferase

p. 249

Steroids

Steroids, lipid Vitamins and terpenes are classified

as isopropenoids.
Chemical structure

Isoprene
(2methyl1,3butadiene)

Carbon backbone

Isoprene unit

p. 264

Structures of
several steroids
Basedon5Cisopropene
3X6Cring+1X5Cring
Cholesterol:OHatC3
Cardiovasculardisease
MammalianHormones
Bileslat
Plantsterols
Cellmembranecomponent

p. 265

Cholesteryl ester

Cholesterolisconvertedtocholesterylestersforstorageincellsorfor
transportthroughthebloodstream.
Sinceinsolubleinwater,cholesterolanditsestersmustbecomplexedwith
phospholipidsandamphipathicproteinsinlipoproteinsfortransport.

p. 267

Myricyl palmitate, a wax

Waxes
nonpolarestersoflongchainfattyacidsandlongchainmonohydroxylicalcohols
protectivewaterproofcoatings
Beeswax,myricylpalmitate,esterofpalmitate(16:0)andthe30Cmyricylalcohol
Earwax,cerumen(fromtheLatinwordcera,wax)
secretedbycellsliningtheauditorycanal
containssqualene,triacylglycerolsandwaxes(about10%oftheweight).
p. 267

Some isoprenoids

Lemonflavor

Archaebacteria
cellmembrane

Developmentregulation
ininsect

p. 268

Flowchart of lipid extraction and purification

p. 269

Biologicalmembrane
Lipidbilayersandproteins
Externalboundariesofcells
Separatecompartmentswithincells
Selectivepumps:transportofionsandsmallmolecules
Generatingandmaintainingtheprotonconcentration
gradientsforATPproduction
Recognizeextracellularsignalsandcommunicatethem
tothecellinterior.

Membrane lipid and bilayer

An amphipathic membrane lipid

Cross-section of a lipid bilayer

5to6nmthick,flexible,selfseal
twosheets,ormonolayers(leaflets)
polarheadgroups:contactwiththeaqueousmedium
nonpolarhydrocarbontails:towardtheinteriorofthebilayer
lipidbilayersisdrivenbythehydrophobicinteractions
p. 270

Typicalbiologicalmembrane
610nm
Lipids:25%~50%
Proteins:50%~75%
Carbohydrate:10%
Cholesterolandsomeotherliplds:~30%oftotallipid
Componentsofinnerandoutermembranesaredifferent.
Redbloodcells:richinproteins
Braincells:richinphosphotidylserines
E.coli:inner70%phosphatidylethanolamines
outerlipopolysaccharides
Mammalian:outersurface90%sphingomylin

Structure of a typical eukaryotic plasma membrane

fluidmosaicmodel:1972S.JonathanSingerandGarthL.Nicolson
membraneisadynamicstructure
proteinsandlipidscanrapidlyandrandomlydiffuselaterallyorrotate
p. 271

Diffusion of lipids within a bilayer

flipflop

2m/sec

2106m/sec

flippasesandfloppases:membraneboundenzymes

generatedandmaintainedlipidasymmetry
ATPdependantmovespecificphospholipidsfromonemonolayertotheother
p. 272

Diffusion of membrane
proteins
1970L.D.FryeandMichaelA.Edidin:
proteinsdiffusewithinthelipidbilayer.
Majorityofmembraneproteinsdiffuse
~100to500timesslowlythanlipids.
Immobilemembraneproteins:
actasfencesorcages,restrictingthe
movementofotherproteins;
producesproteinpatches,ordomains,
areasofmembrane.

p. 273

Freeze fracturing a biological membrane

p. 274

Phase transition of a lipid bilayer.

Thickness
15%

Intheorderedgelstate,thehydrocarbonchainsareextended.
Abovethephasetransitiontemperature,rotationaroundCCbonds
disordersthechainsintheliquidcrystallinephase.
Phasetransitionsinbiologicalmembranescanbelocalized,sofluidandgel
phaseregionscancoexistatcertaintemperatures.

p. 274

Fluidityandphasetransitiontemperature
Thestructureofaphospholipid:incorporatingan
unsaturatedfattyacylgroupintoaphospholipidlowersthe
phasetransitiontemperature.
Cholesterolaccountsfor20%to25%ofthemassoflipidsin
atypicalmammalianplasmamembraneandsignificantly
affectsmembranefluidity.
lipidrafts:
Cholestreolandsphingolipid
Maintainedbymembraneproteins

p. 274

Schematic cross-section of a lipid vesicle,

or liposome

p. 275

Membraneproteins
Integralmembraneproteins
Peripheralmembraneproteins
Lipidanchoredmembraneproteins

p. 271

Bacteriorhodopsin from Halobacterium salinarum

Harness light energy for ATP synthesis

helix
~20aa
lightharvesting
prostheticgroup
(inyellow)

loops
Integralmembraneproteins(transmembraneproteins)
Hydrophobiccore(transmembraneregion)+exposedproteinsonthesurface.
p. 276

Ribbon structure of the transmembrane portion

of porin FhuA from Escherichia coli.

Thisporinformsachannelforthepassageofproteinboundironinto
thebacterium.Thechannelisformedfrom22antiparallelstrands
p. 276

Peripheralmembraneproteins
Associatedwithonefaceofthemembranethrough
chargechargeinteractionsandhydrogenbondingwith
integralmembraneproteinsorwiththepolarheadgroups
ofmembranelipids.
AchangeinpHorionicstrengthisoftensufficientto
removetheseproteinsfromthemembrane.

Lipid-anchored
membrane proteins
attached to the
plasma membrane

(a) A fatty acyl-anchored proteins.

(b) A prenyl-anchored membrane
proteins (prenylated proteins).
(c) Proteins anchored by
glycosylphosphatidylinositol. Outer
leaflet only, and found in lipid
(cholesterol-spingolipid) rafts.

p. 277

MembraneTransport

(Nonpolargases,
Hydrophobicmolecules)

p. 278

ThermodynamicsofMembraneTransport

Aout

inat25C,

[Ain]=1mM, [Aout]=100mM

ThermodynamicsofMembraneTransport
Chargecompounds

:membranepotential(involts)
F :Faradayssconstant(96.485kJV1mol1)
z:chargeonthemoleculebeingtransported

Membrane transport through a pore or channel

pore:forbacteria
channel:foranimals
Noenergyneeded
Notsubstratesaturable
Rateiddiffusioncontrolled
Somealwaysopen.
Someopenorcloseresponseto
signal.
Innervetissue:gatedpotassium
channelrapidoutwardtransport
ofK+10,000timesfasterthan
transportofNa+.

p. 280

Types of passive and active transport.

Uniport

Symport

Antiport

p. 281

Kinetics of passive transport.

MichaelisMentenequation
V0:initialrateofinward
[S]out:externalconcentration
Vmax:maximumrateoftransportofthesubstrate
Ktr:constantanalogoustotheMichaelisconstantKm

p. 281

Passive and active transport protein function.

proteinbindsitsspecificsubstrate

conformationalchange

allowthemoleculeoriontobereleasedon
theothersideofthemembrane

p. 282

Primary active transport

poweredbyadirectsourceofenergy/ATPorlight.

lightharvesting
prostheticgroup
(inyellow)

Bacteriorhodopsin:

useslightenergytogenerateatransmembraneproton
concentrationgradientthatcanbeusedforATPformation.
p. 276

Secondary active transport in Escherichia coli

drivenbyanionconcentrationgradient

Theoxidationofreduced
substrates(Sred)generatesa
transmembraneproton
concentrationgradient.
Theenergyreleasedby
protonsmovingdowntheir
concentrationgradientdrives
thetransportoflactoseinto
thecellbylactosepermease.

p. 282

Secondary-active transport in animals

p. 283

EndocytosisandExocytosis

Movementforlargemolecule,suchasproteins.
Receptormediatedendocytosis:bindingofmacromoleculestospecific
receptorproteinsintheplasmamembraneofthecell,fusingwith
endosomethenwithlysosome.
Exocytosis:materialsforsecretionareenclosedinvesiclesbytheGolgi
apparatus,thenfusewiththeplasmamembrane,releasingthevesicle
contentsintotheextracellularspace.
p. 283

TransductionofExtracellularSignals
Signals:
chemotaxis
hormones
neurotransmitters
growthfactors

TheHotSpiceofChiliPeppers
Vanilloid(capsacin)receptor(inactive)
Opiod
( )
Vanilloidreceptor(active)

Na+andK+flowintonervecell
Pain,temperatureincreasing

General mechanism of signal transduction

across the plasma membrane of a cell.
Gproteinsaresignaltransducers

Cascade:seriesamplificationevents

p. 285

Summary of the adenylyl cyclase signaling pathway

p. 288

Hydrolysis of GTP to GDP and Pi

Gproteinshave
GTPaseactivity

p. 286

G-protein cycle

:fattyacylanchoredprotein
:prenylanchoredprotein

http://upload.wikimedia.org
p. 286

Production and inactivation of cAMP

Thecyclicnucleotides3,5cyclic
adenosinemonophosphate(cAMP)and
itsguanineanalogcGMParesecond
messengersthathelptransmitsignals
fromexternalsourcestointracellular
enzymes.
Methylatedpurinescaffeineand
theophyllineinhibitcAMP
phosphodiesterase.

p. 287

Activation pf protein kinase A

Theassembledcomplexis
inactive.
WhenfourmoleculesofcAMP
bindtotheregulatorysubunit
(R)dimer,thecatalyticsubunits
(C)arereleased.

p. 288

Activation of receptor
tyrosine kinases
Insulin receptor

p. 291

Insulin-stimulated formation of phosphatidylinositol

3,4,5-trisphosphate PIP3

insulinreceptorsubstrates
p. 292

PIP2 produces two 2nd messengers, IP3 and

diacylglycerol.
IP3diffusestothe
endoplasmicreticulum,
whereitbindstoand
opensaCa2+channelin
themembrane,releasing
storedCa2+.
Diacylglycerolremains
intheplasma
membrane,whereit
alongwithCa2+
activatestheenzyme
proteinkinaseC(PKC).

p. 289

Inositolphospholipid signaling pathway.

p. 290