Structural Lipids in Membranes 348 Lipids as Signals, Cofactors, and Pigments 357 Working with Lipids 363 --:; substance, separated from the salifiable bases, olved in boiling alcohol. On cooling, it was crystallized and very pure. and in this state it - amined. As it has not been hitherto described ... - to call it margarine, from the Greek word gpearl. because one of its characters is to have --earance of mother of pearl, which it communicates - ='al of the combinations of which it forms with the - bases. -tvfiche/Eugene Chevreul. article in Magazine, 1814 _igicallipids art' a chemirally diverse grollp of cotn .mds, the common aml defining feal me uf which _ insolubility in water. The biological funcLions of _,ls are as (!i\'(:rse as their chemistry. FMs alld oils '. e principal stored forms of energy in many or s. Phospholipids and sterols are major structural lS of biological membralles. Other lipids, aI _ 1 present in small quantities, pIa.\ Cl'U "les as enzyme rofactors. electron carrkrs. light ling pigments, hydrophobic anchors for proteins. 'rones" to help membrane proteills fold. emulsi - agents in the digestiw trac(. hormones, and "elllliar messeng0rs. This cl1apter introduces rep lipids of each type. with emphasis on theil' llf.<'11 strucl me and physical properr-ies. We discuss -"'1ergy-yielrling axiLlar-ion of lipids in Chapter 17 and synthesis in Chapter :21. 10.1 Storage Lipids fat.", and oils used almost wuversalh' as stored forms of pnergy in li\-ing organisms 1.1re df'l'ivaLives of fatty acids. The fatty adds are hydrocarbon derivat.ives. a[ about t11e same low oxidation state (r-hat is. as highly reduced) as the hydrocarbons in fossil fuels. The cellu lar oxidation of fatty acids (to CO 2 and H 2 0), like the cOlltrolled, rapid burning of fossil fuels ill internal com hustion engilles, is highly exergonic. We introduce here the structures and nomenclat me of the fatty acids most commonly found ill liviJ1g or ganisms. Two of fatty acid-conta.u1ing compounds, trlacylglyccrols alld \\'axes. are described to illustrate the diversity of structme and physical properties ill this of compounds. Fatty Acids Are Hydrocarbon Derivatives F<'lt ly acids are carbo:-..-ylic acids with hydrocarbon chains from ..j to :3(,\ long (C 4 to In SOl11P fatty acids, this chain is unbranc:l1ed and fully sat urat eel (contains Ill! double honds); in others chain con tains one or more double bonds Cfable 10-1). A few contain tlwee-carbon rings. hydroxyl grollps, or methyl group branches. A simplified nomendature for these C'ornpO\.mds spedfies the chail) length and number of double bonds. separated by a colon: for example, tlle 16-carbon saturated palmitic acid is abbreviated 10:0, and the IS-carbon oleic: acid. with one double bond. is 18:1. The positions of any double bonds are specified by superscript numbers following (delta): a 20-cal'bon fatty acid \\1t11 one double llond betwl?en e-9 and C-IO (C- i being the carboxyl carbon) ,md another between C-J2 and C-13 is c1esignared 20:2(.l9.1::), The- rllOS! commonly occurring fatty acids have even llumbers of carbon atoms in an ullhranchecl chain of 12 to 24 carbons (Table 10-1). As WE' shall SE'E' in Chapter 21 , th p\-en number of carbons resulr-s frCll\l the rnode of 343 344 Chapter 10 lipids synthesis of these compounds, which involves conden They are also procluced during hydrogemtion of nsh sation of t\vo-carbon (acetate) units. vegetable oils. Because diets high ill trans fatty ac There is also a common pattern in the location correlate with increased blood levels of LDL (bad c 01' double bonds: in most monounsaturated fatty acids lesterol) and decreased HDL (good cholesterol), i the double bond is bet\veen 0-9 and 0-10 ancl genera]Jy recommended that one avoid large amOl Llte other double bonds of polyunsaturated fatty acids oJ these fatty acids. Unfortunately, French fries, doug. are generally 11 12 ancl 11 15 . (Arachidonic acid is an nuts, and cookies tend to be high in trans fatty ad exception to (,his generalization.) The double bonds 'fhe physical propenies of the fatty acids, and of polyunsaturated fatly acids are almost never con compounds that contain them, are largely determil jugated (altemating single and double bonds, as in b;y the length and degree of unsaturation of the hva -CH=CH-CH=CH-) but are separated by a meth carbon chain. The nonpolar hydrocarbon chain acCOUL ylene group: -CH=CH-CHz-CH=CH-. In nearly for the poor solubility' of fatty acids in water. Lauric a all naturally occurring unsaturated fatty odds, the dou (12:0, lvJ r 200), for example, has a solubility in water ble bonds ore in the cis configuration. Trans fatty acids 0.063 mg/g-mllch less than that of glucose (M, Ie are produced by fermentation in the rumen of dairy an which is 1 100 rnglg. The longer Ule fatty acyl chain imals and are obtained [rom dairy products and 111eat, the fewer the double bonds. the lower is the solubL.: TABLE 10-1 Some Naturally Occurring Fatty Acids: Structure, Properties, and Nomenclature Solubility at 30C (mg/g solvent) Carbon Common name Melting skeieton Structure Systematic namet (derivation) point (0C) Water Benze E 12:0 CH 3 (CH 2 h o COOH n-Dodecanoic acid Lauric acid 44.2 0.063 2.600 (Lati n laurus. "laurel plant") 14:0 CH3(CH2h2COOH n-Tetradecanoic acid Myristic acid 53.9 0.024 874 (Latin Myristlca, nutmeg genus) 16:0 CH 3 (CH 2 )14COOH nHexadecanoic acid Palmitic acid 63.1 0,0083 348 (Latin palma, "palm tree") 18:0 CH3(CH2h6COOH n-Octadecanoic acid Stearic acid 69,6 0.0034 124 (Greek stear, "hard fat") 20:0 CH 3 (CH 2 hBCOOH n-Eicosanoic acid Arachidic acid 76.5 (Latin Arachis, legume genus) 24:0 CH3(CH2)nCOOH n-Tetracosanoic acid Lignoceric acid 86.0 (Latin lignum, "wood" + cera. "wax") CH3(CH2)5CH=CH(CH2),COOH cis-9-Hexadecenoic acid Palmitoleic acid 1-0.5 18:1(,l9) CH 3 (CH 2 };CH-CH(CH 2 hCOOH cis-9-0ctadecenoic acid Oleic acid 13.4 (Latin oleum. "oW) 9.12) CH 3 (CH 2 )4CH=CHCH 2 CH= cis-,cis-9.12-0ctadecadienoic Linoleic acid 1-5 CH(CH 2 hCOOH acid (Greek finon, "flax") 9,12.15) CH 3 CH 2 CH=CHCH 2 CH= cis-.cis-,cis-9,12.15 a Linolenic acid -11 CHCH 2 CH=CH(CH 2 )7COOH Octadecatrienoic acid
CH3(CH2)4CH=CHCH2CH= cis-,cis-,cls-,cis-5,8,11, 14 Arachidonic acid -49.5 CHCH 2 CH=CHCH 2 CH= Icosatetraenolc acid CH(CH2)3COOH "Ali aCids are shown," I el, nonlonized form, A: pH 7, all free fally acids have an .onized carbo,ylale. 'ote Ihat numbering of carbon atoms begins allhe carboxyl carbon. lThe prefix n indicates the "oormal" unbranched structure, For Instance, "dodecanoic simply indicates 12 carbon atoms, WhIch could be arranged In a vaJlety of brancheC forms; "ndodecanolc the linear, unbranChed form. For unsaturated fatty acids, tile configuration of each double bond Is Indicated: in oiologioal fatty acids the oon iguratlon is almost cis. 10.1 Storage Lipids 345 (b) arboxyl JUp f "':, ...drocarbon ;ain
(d) :'iatul'aleu ".Htyacids E 10-1 The packing oj fatty acids into stable aggregates, The - packing depends on the degree oi satur<ltion. (a) 1''''0 rep -"o'1s Drlhe iully S<llurilted acid ,teari, acid ',stearate at pH 7i ;;ual extended coniofrnation. Each line segnwnl oi the zigzag a single bond between adjacent carbons, (b) 'nlC cis dOll 'd rshaded) in oleic acid loleate) doE'.s not permit rotation and ces a rigid bend In the hydrocarbon tail. All olher bonds in the ..e free to rot,lIe. (c) Fully saturated latty dclds in the extended ck inlo heady crystililine arrays. stabilized by many h>'dro. Interaclions, (d) The presence 01 one or more cis double bonds c'b w'ith this tight packing ilnd re,ults in less slabIe aggregates. -81'. The carboxylic acid group is polar (and ion 1 neur-ral pH) and <'!(;COUllts for the slight, solubil . short-chain fatty acids in water, elting poims are also s\,rong1;y influenced by the . -h and degree of unsat,uration of the hydrocarbon .-\t room temperature (25C), the saturated fatty rom 12:0 to 24:0 have a waxy consistency. whereas "ll.rated fatty acids of these lengths are oily liquids. difference in rnelt.irlg points is due to different de -, of packing of the fatty acid molecules (Fig. 10-1). de fUlly saturated compounds, free rotation around carbon-carbon bond gives the. hydl'Ocarhon chain flexibility; the most stable is tile fully lded form, in which the steric hindrance of neigh -..5 atoms is minirnizecl. These molecules can pack to er tightly in nearly clystalline arrays, \\ith ,)tOlns all g their lengt,hs in van del' Waals contact with the !-, of neighborirlg rnolecules. In unsaturated fatty ..l, a (:is double bond forces a kink in the hyc1rocar ('hain. Fatty adds wit]1 one or several such kinks Mixture of saturated and unMturated fatty acids caJUlOt pack toget.her as tightly as fully saturated fatty acids, and their interactions with each other ar<:' t.here fore weaker. Because it takes less thermal energy to disorder these poorly ordered arrays of unsaturated ratily acids. t.hey have markedly lo"ver melting points than saturated fatty acids of the same chain length Crable 10-1). In vert,ebrates, free fatty' acids (u1l6sterified fatty acids, with a fTee c2rboxylate group) circulate in the blood bound nOl1covalemly to a protein carrier, sel'\lm albumin. How-ever, fatty acids are present in blood plasma mostly as carboxylic: acid derivatives such as es ters or amides. Lacking the charged carhoxylate group, these fatty acid derivatives are generally even less sol uble in water than are the free [aU.y acids. Triacylglycerols Are Fatty Acid Esters of Glycerol The simplest bpids constructed from fatLy acids are the triacylglycerols, also referred to as triglycerides, fats, or neutral fats. Triacylglycerols are composed of t,hree fatty acids each in ester linkage \"'ith a single glycerol (Fig. 10-2). Those containing the same kind of fatty acid CH 2 / " / " HO CH OR
Glycerol )C{f2 -f 0 C-O O-C 0=)
l-Stearoyl. 2-1inoleoyl, 3-palmitoyJ glycel'ol. a mi.-.;ed triacylglycerol AGURE 10-2 Glycerol and a triacylglycerol. The mixed triacylglyc erol shown here has three difierenl iatty acids attached to Ihe glyc erol backbone. '1Alhen glvcerol has two dliierenr iatly acids at C-l ,lIlel C3, the C-2 is a chirill center (p, 76i, 346 Chapter 10 Lipids in all three positions arE' called simple and are namE dafter tl18 fatty acie! th .' ("omain. Simplo tliacylglycerols of 16:0. 18:0, and 18: 1, for e,ample, are tristearin trilJalmitin, and triolein, respectively. Most naturally occurring triacylglycerols are mixed: C011 tain t\VO or more differenT fatty acids, To name these compollnds unamuiguollSly, tlle narne and position of each fatty acid must be specified. Because tJle polar hydrox ls of glycerol 0111(1 the polar carboxylates of the fatty acids are bound in ester linkages. triacylglycerols are nonpolar, hydrophobic mol pcules, essentially insoluble in water. Lipids have lower specific gravities than wat,er. explains why TILL\. turf'S of oil and water (oil-nncl-vinegar salad clressing. for e 'ample) hm e two phases: oil with the lower specific gravity, floats on the aqueous phase. Triacylglycerols Provide Stored Energy and Insulation In most eukaryolic cells, triacylglycerols form a sepa rate phase of microscopic. olly droplets in t.he aqueous cytosoL servi11g as depots of m fuel. III verte brates, specialized cells called adij)ocytes, or far cells. store large <llnounts of triarylglycerols as fat droplets that nearly lill the cell (Fig, 10-3a) Triacylglycel'ol<; are also stored as oils ill tIle seeels of many types of plants, providing energy and hiosynthetic precursors cluriJlg seed gel'minat'ioll (Fig. 1 .. dipocytes and genni \lating seeds contain lipases, ell2, "mes that catalyze the hy"drolysis of slored tl'iacylglycerols. releasing fat.L Y ' acids for export to sites where they are required as fllel. There are two significant advamages t,o using tria cylglycerols as st,ored fllels. rather than polysaccllarides such as and starch. First. hec.ausc the carhon atoms of fatL:v' acids are more rednceel than tl,ose of sug ars, oxidation of e1"01s yields tno]'(> thAn twice as much energy, gram for gram. as the o:-.iclatioll of car bohydrates. Second, because are hy drophobic and r,lterefore unhydrnted, tlp organism tlttJt carries fat- aB fuel does not have to can':v' the exLra weiglJt of water of hydration thaL is associated with storeel poly saccharides (2 g per gram of pol:fsaccharide), Humans haw fat tissue (r:ornposed primarily of adipocyt'('s) UIl cler lhe skin. in the abdominal cavity, and in the mam nwry glands. 1Vloderately obese people with 151.0 20 kg of triacylglyce]'o)s depositeel in their es could meet their energy needs for month by drawing on their fat stores. In comrasL the hum.an call store less than a day's ellergs supply in form of glycogen. Car bohydrates snch a.s glucose and glycogen 10 offer cer tain advantages as quick sources of metabolic energy, onE' of which is Ulcir ready solubilit:v' in wat er. III some anilnals) tr1.acy'lglycerols stored lUlder tlle skin sen e not. only as energy stores but as insulation against low temperatures, Seals. w(l]ruses. penguins. and ot,her warm-blooded polar aJlinw]s arE' ampb i paddeel with triacylglycerols. In hibernatulg animals (bears, for f-- (a) 8 M-m FIGURE 10-3 Fat stores in cells. (a) Cros, section of jour guin 3dipoc)'tes. shoIVing huge tal droplets lh"t vil,tual1r fill the cells. visible ,1re severill capillarics in crOss section. (b) ero" '"clion cot),lec!()n cell !rom a seed of the plant Arabi(/opsis. The strUctUrcs are protein bodies. which are -urrounded b' ,tored Qlb the light- nlored oil bodies. example), the huge fnt. re::;erves aCClU1lUlatCc! b fL hibenlation serve Ihe dual purposes 01' insulation energy storagE' (see Box 17-1). The low density of acylglycerols is the basis fo]' euwther remarkable fur t.ion of thesE' c "lmpounds. In sperm \\"ha]es, ,1 triacylglycerob and waxes allows the allimals t.o maL tIp Ilcy of their bodifs to that of tlleir surroun ings during deep clives in cole! water (Box in-I). Many Foods Contain Trlacylglycerols Most natural fats, such as those ill i'egeti1ble oils. dai2 pro luets. and <Uuma! fat" are complex: wi-tures of -in pie and mixed triar:ylglycerois. These contain a varie of acids cUffering in chain length anel degree of sa urCition (Fig. 10-4). \egewble oils such as com (lllaiz F ami olive oil are composed largely of 'ero \\"itll unsa! uratp.d fatt.y acids and thus are liquids at roo temperature, The.. ar collverted into soli ------ 10.1 Storage LipIds 347 BOX 10-1 THE WORLD OF BIOCHEMISTRY rm Whales: Fatheads of the Deep ....es of sperrn ,;vltales have uncovered nnot]lPr way !lilh triacylgJycerols are biologically useful. The 1 whale's head is very 1m'ge, accoillltin,g for over -llirrl of its total body weight. About 90% of the of the head is madE' up of the spermaceti or a blubbery mass that cont.ains up to kg J[ 4 LOns) of spennacptj on, a mixture of tdacyl ,rols and waxes containing an abundance of un aled fal ty acids. TIlls mixture is liquid ar The :: ml reshng body temperature of the vvhale, abollt - but it. begins to crystallize at. about 31 "C and 'TIes soliu when the ternjJcraturc drops several _. degreps. -:'he probable biological function of spermaceti oil cpn deduced from research 011 the anatomy ancl 19 behavior of the spenn "vhale. Thcse mammals almost 0xclusively on squiclln very deep waleI'. eif feecling clives (hey descend 1,000 m or more; leepe.<;\ recorded clive is 3,000 m (almost 2 miles). ese depths, there are no competitors for the iful sqtLicl; Ute :'lperm whale rests quictly, waiting chools oJ squid to pass. For a marine animal to remain at a gjven depth ut a constant swirrlIning effort, it must have the density as the smwundlng water, The sperm f' LU lclergoes changes in buoyancy to match the fly uf its sum;>undillgs-from the tropical ocean -ace to great depths wherc the water is much colder ;;iml thus denser. The key is the freezing point of spermaceti oi1. the temperature of t.he oil is [owerecl several degrees during a deep dive, it con geals or crystallizes and becomes denser. Thus U1E'. buoyancy of the whale c]1i:U1ges to match the density of seawater. Various physiological mechanisms pro mote rapid cOoling of Lhe oil during a dive. DuriI)g the return to rhe surface, the congealed spermaceti oil warms and melts, decreasing its density to match that of the surface water, Thus we see in the sperm whale a remarkable anatomical and biochemical adaptation. The triacylgb-cerols ancl 'waxes synthesized by the sperm whale contaill fatly acids of the necessary chain lengtb and degree of lmsaturation to give the sper maceti oil tl10 proper melting point for the animal's diving habits. UnJort.llilately for the sperllI whale pOj)ulatioll, spennacf>ti oil waS at one lime considerect the finest lamp oil and continues to be (;oITunercially w11nable as a lubricant, Several centuries of intensive hunting of these manmlals have driven SPeI111 whales onto the endangered spedes list. Spermaceti organ r catnlytic hydrogenation, whk'h reduces some U' double bonds to single bouds and converts oth G'ans d<mble bonds. Triacylglycerols containing tunned fatty acids, such as tristeari]l, rhe major /lent of beef fat, are 'wltite, greasy solids at, room :>nHme .neIl lipid-rich foods are exposed too long to the ill air, they may spoil and become rancid, The aflRnt taste and slTlell associated with rancidity rc the oxidative cleavage of the double bonds ill _"E 10-4 Fatly acid composition of three food fats, Olive Oil. .and beef iat consiq of mixtures oj tri,1Cylglycerols, differing in 'all\' "cid COlllpo'llioi"l. The melting points ot these e their physiCLlI statc at room temperature 125 CO_are a r1irec n 01 their 1,111)/ acid compOSition. Olive oil has a high propm. -; long-chain Ie", ilnd C'6) unsaturated latty acids, which ac , for its liquid state at 2S 'C The higheJ proportion of lung-chain .. C 16 and C,e C'6 and C 4 tel C, I saim'ated uJUll\lurated saturated 'oor 80 I -;; 60 <:I :g I .;:;. 40 ... 20 l I nd C16) saturated fattv <1cids in butter increases its melting point . lter is it soft solid at rQom lempcr,llure. Beef fat with all even er proportion 01 long-chai n saturated iall\" (lClds, is ,1 hard solid. 348 Chapter 10 Lipids ullsaturated fatty acids, which produces aldehydes and carboxylic acids of shorter chain length and therefore higher volatility. Waxes Serve as Energy Stores and Water Repellents Biological wa cs are esters of long-chain (C 14 to C: 16 ) satLU'8ted amI lmsaturated fatty acid \ tIl long-chain (ell; to C 30 ) alcohols (Fig. 10-5). Their melting points (60 to 100C) are genE:'rally higher than those of tria cylglycerols. 1n plankton, the free-floati.ng microorgan isms at t.he bottom of the food chain for marine animals, waxes are the chief storage form of met,abolic fuel. \Vaxes also serve a diversity of other functions re lat.ed to tl1cir water-repellent prop .rUes ann their firm consistency. Ccrt<lin skin gJ,mcls of vertebrates liecrete waxes to prated hail' am1 skill and keep it. pliable, lu bricated, and waterproof. Birds, p31ticlllarly waterfowl, Sf'(Tete 'waxes from their preen glands to keep their feathers water-repellent. The shillY leaves of 11 ally, rhodockndrons, poison ivy, and nWlIY t.ropical plants are coated with a thick layer of waxes, which prevents e.;'cessive evaporation of water and protects agaillst parasites. Biological vv'axes fillCl a variety of applications in the pharmaceutical, cosmetic, ,md other industries. TJanolin ([rom lamb's wool). beeswax (Fig. 10-5), CaJ'nauba wax (from a Brazilian palm tree). and wa . extracted from spermaceti oil (from whales; see Box 10-I) are widely llsed in th manufacture of lotions, ointments, and polishes. o II 14-C-O-CH2-(CH2 ...J)\ J Palmitic acid I-Triacontanol (a) (b) FIGURE 10-5 Biological wax. (a) Triacontanoylpahnitate. the major component oi beeswax. is an ester of palmitic acid with the alcohol tri,lcont,Jnol. (b) i\ honeycomb, constructed of beeswax, is iirm at 25( and completely impervious to waler. The term "wax" originates in Ihe Old English I'veax. meaning "the material of the hOlleV(omb," SUMMARY 10.1 Storage Upids Lipids are water-insoluble cellular componep of cUyerse structure that can be extracted b, nonpolar solvents, Almost all fatty acids, the hydrocarbon components of many lipids, have an even number of carbon at.OIns (usually 12 to 24)' are either saturat.ed or w1satmat-ed, with clOl t bonds almost always in the cis configuration. 1'riacylgly erols contain three fatty acid molecules estelified to t.he thrce hydrox..yl groups of glycerol. Simple triacylglycero!s contain only one type of fatty a ie!; mixed triacylglycerols, t"vo or rhree types. Triacylglycerols are pri.marily storage fats: they <"Ire present in many foods. 10.2 Structural Lipids in Membranes The cent.ral architectural feature of biological r branes is a double layer of lipids, which acts as a riel' to the passage of polar molecules a.nd ions. :'le_ branE lipids are amphipathic: one end of the moleCl... is hydrophobic, the other hydrophilic. Their hydroph bic interactions "ilh each other and their hydropru:.. interactions v..ith water direct their packing into she called membrane bilayer:,;, In this section we desclil five general types of membrane lipids: glycerophos P lipids, U1 whkh the hydrophobic: regions are comp of two fatty acids joined to glycerol; galact.olipids a! sulfolipicls, which also contain two fatty acids esterifi t,o glycerol, but. lack t,he characteristic phosphat.e of ph pholipicis; archaebaeterial tetraether lipids, in which tv very long alkyl chains are et.her-linked to glycerol at bo' ends; sphingolipids, in which a sutgle fatty acid is joine to a fatty amine, sphingosine; and sterols, compOUl1 chant -terized by a rigid sy::;t.em of fom fused hyclro a . bOll rings. The hydrophilic moieties iII these amphipathic: cop- pOlmds may be as simple as a single -OH group one elld of the sterol ring sylitem, or the; may be mu more complex. In glycerophospholipids and some sphiI golipids\ a polar head group is joined to t.he hydro h bie moiety by a l)hosphodiest.er linkage; these are th phospholipids. Other sphingolipids lack phosphate bu' ha.ve a simple sugar or compl"'x oligosaccharide at t.heir polar ends; these are t.he glycolipids (Pig. 10-6). Withir t.hese groups of membrane Upids, enormous diversity re sults from various combulations of fatty acid "tails" an' polar "heads," The arrangeme1\t of these lipids in mem, branes, and their St.nlC ural and fUlictiOIlClI roles thereill are considered in the next, chapLer.