FATTY ACIDS: METHYLENE-INTERRUPTED DOUBLE BONDS

Transcription

1 Ftty cids: methylene-interrupted double bonds - structures, occurrence nd biochemistry FATTY ACIDS: METHYLENE-INTERRUPTED DOUBLE BONDS STRUCTURES, OCCURRENCE AND BIOCHEMISTRY Structure nd Nomenclture The lipids of ll higher orgnisms contin pprecible quntities of polyunsturted ftty cids ( PUFA ) with methyleneinterrupted double bonds, i.e. with two or more double bonds of the cis-configurtion seprted by single methylene group. CH CH CH CH2 CH The term homo-llylic is occsionlly used to describe this moleculr feture. In higher plnts, the number of double bonds in ftty cids only rrely exceeds three, but in lge nd nimls there cn be up to six. Two principl fmilies of polyunsturted ftty cids occur in nture tht re derived biosyntheticlly from linoleic (9-cis,12-cis-octdecdienoic) nd α-linolenic (9-cis,12-cis,15-cis-octdectrienoic) cids. linoleic cid COOH α-linolenic cid COOH In the shorthnd nomenclture, these re designted 9c,12c-18:2 nd 9c,12c,15c-18:3 respectively. The number before the colon specifies the number of crbon toms, nd tht fter the colon, the number of double bonds. The position of the terminl double bond cn be denoted in the form (n-x), where n is the chin-length of the ftty cid nd x is the number of crbon toms from the lst double bond, ssuming tht ll the other double bonds re methylene-interrupted. Thus linolete nd α-linolente re 18:2(n-6) nd 18:3(n-3), respectively (18:2ω6 nd 18:3ω3 in the older literture). Both of the prent ftty cids cn be synthesised in plnts, but not in niml tissues, nd they re therefore essentil dietry components (see below). Polyunsturted ftty cids cn be found in most lipid clsses, but they re especilly importnt s constituents of the phospholipids, where they pper to confer distinctive properties to the membrnes, in prticulr by decresing their rigidity. The exception is the sphingolipids, where they re rrely detected in other thn trce mounts. The (n-6) Fmily of Polyunsturted Ftty Acids Linoleic cid is ubiquitous component of plnt lipids, nd of ll the seed oils of commercil importnce. For exmple, corn, sunflower nd soyben oils usully contin over 50% of linolete, nd sfflower oil contins up to 75%. Although ll the linolete in niml tissues must be cquired from the diet, it is usully the most bundnt di- or polyenoic ftty cid in mmmls (nd in most W.W. Christie 1

2 Ftty cids: methylene-interrupted double bonds - structures, occurrence nd biochemistry lipid clsses) typiclly t levels of 15 to 25%, lthough it cn mount to s much s 75% of the totl ftty cids of hert crdiolipin. It is lso significnt component of fish oils, lthough ftty cids of the (n-3) fmily tend to predominte in this instnce. Anlogues of linoleic cid with trns-double bonds re occsionlly found in seed oils. For exmple 9c,12t-18:2 is reported from Dimorphothec nd Crepis species, nd 9t,12t-18:2 is found in Chilopsis lineris. The remining members of the (n-6) fmily of ftty cids re synthesised from linolete in niml nd plnt tissues by sequence of elongtion nd desturtion rections s described below. Shorter-chin components my lso be produced by lph or bet-oxidtion. Most cn function s essentil ftty cids. γ-linolenic cid ( GLA or 6-cis,9-cis,12-cis-octdectrienoic cid or 18:3(n-6)) is usully minor component of niml tissues in quntittive terms (< 1%), s it is rpidly converted to higher metbolites. It is found in few seed oils, nd those of evening primrose, borge nd blckcurrnt hve some commercil importnce. Evening primrose oil contins bout 10% GLA, nd is widely used both s nutrceuticl nd medicl product. 8-cis,11-cis,14-cis-Eicostrienoic cid (dihomo-γ-linolenic cid or 20:3(n-6)) is the immedite precursor of rchidonic cid, nd of fmily of eicosnoids (PG 1 prostglndins). However, it does not ccumulte to significnt extent in niml tissue lipids, nd is typiclly bout 1-2% of the phospholipid ftty cids. Archidonic cid (5-cis,8-cis,11-cis,14-cis-eicostetrenoic cid or 20:4(n-6)) is the most importnt metbolite of linoleic cid in niml tissues, both in quntittive nd biologicl terms. It is often the most bundnt polyunsturted component of the phospholipids, nd cn comprise s much s 40% of the ftty cids of phosphtidylinositol. As such, it hs n obvious role in regulting the physicl properties of membrnes, but the free cid lso is involved in the mechnism by which poptosis is COOH regulted. Severl fmilies of eicosnoids re derived from rchidonte, including prostglndins (PG 2 series), rchidonic cid thromboxnes, leukotrienes, nd lipoxins, with phosphtidylinositol being the primry source. These hve n enormous rnge of essentil biologicl functions tht re discussed in elsewhere in these web pges. In ddition, 2-rchidonoylglycerol nd nndmide (N-rchidonoylethnolmine) hve importnt biologicl properties s endocnnbinoids, lthough they re minor lipids in quntittive terms. While rchidonte is found in ll fish oils, polyunsturted ftty cids of the (n-3) fmilies tend to be present in much lrger mounts. Archidonic cid is frequently found s constituent of mosses, liverworts nd ferns, but there ppers to be only one definitive report of its occurrence in higher plnt (Agthis robust). The fungus Mortierell lpin is commercil source or rchidonte vi fermenttion process. 4,7,10,13,16-Docospentenoic cid (22:5(n-6)) is usully reltively minor component of niml lipids, but it is the min C 22 polyunsturted ftty cid in the phospholipids of testes. It cn mount to 70% of the lysobisphosphtidic cid, for exmple. In this instnce, C 22 ftty cids of the (n-3) fmily re present t reltively low levels, in contrst to most other reproductive tissues. Other ftty cids of the (n-6) fmily tht re found in niml tissues include 20:2(n-6), 22:3(n-6) nd 22:4(n-6). The lst of these, 7,10,13,16-docostetrenoic or drenic cid, is significnt component of the phospholipids of the drenl glnds nd of testes. Tetr- nd pentenoic ftty cids of the (n-6) fmily from C 24 to C 28 hve been found in testes, nd even longer homologues occur in retin. Very-long-chin ftty cids were first reported from humn brin in ptients with the W.W. Christie 2

3 Ftty cids: methylene-interrupted double bonds - structures, occurrence nd biochemistry rre inherited disorder, Zellweger's syndrome, but it ws subsequently demonstrted tht such ftty cids with up to 38 crbon toms nd with from 3 to 6 methylene-interrupted double bonds re present t low levels the brin of norml young humns, with 34:4(n-6) nd 34:5(n-6) tending to predominte. The function of these is not known. Until recently, the most highly unsturted ftty cid of the (n-6) fmily ws believed to be 28:7(n- 6) (4,7,10,13,16,19,22-octcosheptenote), which hs been found in the lipids of mrine dinoflgelltes nd herring muscle. Now, 4,7,10,13,16,19,22,25,28-tetrtricontnonenoic cid (34:9(n-6)) hs been identified in the freshwter crustcen species Bthynell ntns. The (n-3) Fmily of Polyunsturted Ftty Acids α-linolenic cid (9-cis,12-cis,15-cis-octdectrienoic cid or 18:3(n-3)) is mjor component of the leves nd especilly of the photosynthetic pprtus of lge nd higher plnts, where most of it is synthesised. It cn mount to 65% of the totl ftty cids of linseed oil, where its reltively susceptibility to oxidtion hs prcticl commercil vlue in pints nd relted products. In contrst, soyben nd rpeseed oils hve up to 7% of linolente, nd this reduces the vlue of these oils for cooking purposes. α-linolenic cid is the biosynthetic precursor of jsmontes in plnts, which pper to hve functions tht prllel those of the eicosnoids in nimls. In niml tissue lipids, α-linolenic cid tends to be minor component (<1%), the exception being grzing non-ruminnts such s the horse or goose, where it cn mount to 10% of the dipose tissue lipids. As with linolete, the remining members of the (n-3) fmily of ftty cids re synthesised from α-linolente in niml nd plnt tissues by sequence of elongtion nd desturtion rections s described below, while shorter-chin components my lso be produced by lph or betoxidtion. They re essentil ftty cids. 11,14,17-Eicostrienoic cid (20:3(n-3)) cn usully be detected in the phospholipids of niml tissue but rrely t bove 1% of the totl. Somewht higher concentrtions my be found in fish oils. Steridonic cid (6,9,12,15-octdectetrenoic or 18:4(n-3)) is occsionlly found in plnts s minor component, nd it occurs in lge nd fish oils. 3,6,9,12,15-Octdecpentenoic cid or 18:5(n-3) is significnt component of the lipids of dinoflgelltes, nd it cn enter the mrine food chin from this source. 8,11,14,17-Eicostetrenoic cid (20:4(n-3)) is found in most fish oils nd s minor component of niml COOH phospholipids. It is frequently encountered in lge nd mosses, but rrely in higher plnts.5,8,11,14,17- Eicospentenoic cid ( EPA or 20:5(n-3)) is one of the most importnt ftty cids of the (n-3) fmily. It occurs eicospentenoic cid (20:5(n-3)) widely in lge nd in fish oils, which re mjor commercil sources, but there re few definitive reports of its occurrence in higher plnts. It is n importnt constituent of the phospholipids in niml tissues, especilly in brin, nd it is the precursor of the PG 3 series of prostglndins nd resolvins, which hve nti-inflmmtory effects (see the pproprite web pge). There is currently gret interest in the role of this cid in treting neurologicl disorders such s schizophreni. 7,10,13,16,19-Docospentenoic cid (22:5(n-3)) is n importnt constituent of fish oils, nd it is usully present in niml phospholipids t level of 2-5%. W.W. Christie 3

4 Ftty cids: methylene-interrupted double bonds - structures, occurrence nd biochemistry 4,7,10,13,16,19-Docoshexenoic cid ( DHA or 22:6(n-3)) is usully the end point of α-linolenic cid metbolism in niml tissues. It is mjor component of fish oils, especilly from tun eyeblls, nd of niml phospholipids, those of brin synpses nd retin contining prticulrly high proportions. Indeed, there is evidence tht incresed levels of this ftty cid re correlted with improved cognitive nd behviourl function in the development of the humn infnt. Dietry supplements my lso benefit the elderly. While DHA is found in high concentrtions in mny species of lge, especilly those of mrine origin, it is not present in higher plnts. COOH docoshexenoic cid DHA is not substrte for the prostglndin synthse/cyclooxygense enzymes, nd indeed it inhibits them. However, vi the ction of lipoxygenses, it is the precursor of the docosnoids, termed resolvins or protectins, which re nlogous to the eicosnoids nd hve potent ntiinflmmtory nd immuno-regultory ctions. The concentrtion of DHA in tissues hs been correlted with number of humn disese sttes, nd it is essentil to mny neurologicl functions. Prticulr ttention hs been given to its role in the retin where it is mjor structurl component of the photoreceptor outer segment membrnes. For exmple, it binds strongly to specific sites on rhodopsin, the primry light receptor in the eye, modifying its stbility nd ctivity. It ffects signlling mechnisms involved in phototrnsduction, enhncing ctivtion of membrne-bound retinl proteins, nd it my be involved in rhodopsin regenertion. In some cses, sight defects hve been meliorted with DHA supplementtion. It is intimtely involved with phosphtidylserine metbolism in neuronl tissue. DHA is believed to hve specific effects on gene trnscription tht regulte number of proteins involved in ftty cid synthesis nd desturtion, for exmple. It hs been demonstrted to hve beneficil effects upon inflmmtory disorders of the intestine nd in reducing the risk of colon cncer, which my be medited through ssocitions with specific signlling proteins in membrnes. As phospholipid constituent, it hs profound effects on the properties of membrnes, modulting their structure nd function. In such n environment, DHA is believed to be more compct thn more sturted chins with n verge length of 8.2Å t 41 C compred to 14.2Å for oleic chins. This is the result of doption of conformtion with pronounced twists of the chin, which reduce the distnce between the ends. The methyl group with its extr bulk is locted in the interior region. In mixed-chin phospholipids, further consequence is mrked increse in the conformtionl disorder of the sturted chin. There ppers to be n incomptibility between the rigid structure of cholesterol nd the highly flexible chins of DHA, promoting the lterl segregtion of membrnes into PUFA-rich/cholesterol-poor nd PUFA-poor/cholesterol-rich regions. The ltter my ultimtely become the membrne microdomins known s rfts. PUFA-rich/cholesterol-poor membrne microdomins re techniclly less esy to study thn rfts, but they my lso contin distinctive proteins nd hve importnt biologicl functions. It hs been proposed tht chnges in the conformtion of signlling proteins when they move between these very different domins my hve the potentil to modulte cell function in mnner tht my explin some of the helth benefits of dietry consumption of DHA. Other ftty cids of the (n-3) fmily tht re found in nture include 22:3(n-3) from niml tissues nd 16:3(n-3), which is common constituent of lef lipids (see our web pges on mono-nd diglctosyldicylglycerols). 16:4(n-3), 16:4(n-3), 21:5(n-3), 24:5(n-3) nd 24:6(n-3) re W.W. Christie 4

5 Ftty cids: methylene-interrupted double bonds - structures, occurrence nd biochemistry occsionlly present in mrine orgnisms, including fish. Heptenoic ftty cids of the (n-3) fmily (38:7(n 3) nd 40:7(n 3)) hve been reported from brins of ptients with defined genetic defect, but the most highly unsturted ftty cid of the n-3 fmily yet found is 4,7,10,13,16,19,22,25- octcosoctenote (28:8(n-3)) from mrine dinoflgelltes. The (n-9) Fmily of Polyunsturted Ftty Acids Olete cn be chin elongted nd desturted in niml tissues with 5,8,11-eicostrienoic cid (20:3(n-9) or Med s cid ) s the most importnt product. This only ccumultes in tissues when the nimls re suffering from essentil ftty cid deficiency (see below). Other ftty cids of this fmily tht my lso be found t low levels include 18:2(n-9), 20:2(n-9) nd 22:3(n-9). Other Fmilies of Polyunsturted Ftty Acids 9,12-Hexdecdienoic cid (16:2(n-4)) is found in mrine microorgnisms nd is presumbly the biosynthetic precursor of other ftty cids with n (n-4) terminl structure, i.e. 18:2(n-4), 20:2(n-4), 16:3(n-4) nd 18:3(n-4). Ftty cids of n (n-1) fmily, lso found in mrine orgnisms, re believed to be derived biosyntheticlly by further desturtion ( 15) of 6,9,12-hexdectrienoic cid (16:3n-4)). The min nturlly occurring ftty cids of this type re 16:4(n-1) nd 18:4(n-1), but 18:5(n-1) hs lso been detected. Trce mounts of polyunsturted ftty cids of n (n-7) fmily re occsionlly encountered in tissues nd re presumbly metbolites of 9-16:1. Biosynthesis of Linoleic nd Linolenic Acids Linoleic nd α-linolenic cids re synthesised in plnt tissues from oleic cid by the introduction of double bonds between the existing double bond nd the terminl methyl group by the sequentil ction of 12 nd 15 desturses. 9-18:1 n-9 12 desturse 9,12-18:2 n-6 15 desturse 9,12,15-18:3 n-3 The min substrte for the 12 desturse is 1-cyl,2-oleoyl-phosphtidylcholine in the endoplsmic reticulum of the cell (lthough other lipids my lso be substrtes in chloroplsts). The newly formed linolete is then trnsferred by vriety of mechnisms to other lipids. Phosphtidylcholine cn lso be the substrte for further desturtion, but in lef tissue in number of plnt species it ppers tht most α-linolente is formed by desturtion of linoleic cid linked to monoglctosyldicylglycerols. Those plnts tht produce significnt mounts of 16:3(n- 3) dd further complictions to the problem, nd it is evident tht much remins to be lerned of the overll process. In fct, two distinct desturses hve been chrcterized tht cn insert the 12 double bond, i.e. plstidil enzyme (FAD6), which uses the terminl methyl group s reference point nd is n ω6 desturse s it introduces the double bond six crbons from the terminl crbon, nd secondly n extr-plstidil olete 12 desturse (FAD2) tht is selective for C-12,13 oxidtion independently of chin length. The ltter is relted closely to n enzyme in the seeds of cstor oil (Ricinus communis) tht converts olete to (R)-12-hydroxysterte. Indeed, whether the product is hydroxyl group or double bond my depend on the nture of only four mino cid residues. Less is know of the desturse (FAD3) tht converts linolete to α-linolente, but it is rgued tht it W.W. Christie 5

6 Ftty cids: methylene-interrupted double bonds - structures, occurrence nd biochemistry should be considered s n ω3 rther thn s 15 enzyme. It lso hs much in common with hydroxylse enzymes. Infrequently in plnts, double bond is inserted between n existing double bond nd the crboxyl group s in the biosynthesis of γ-linolenic cid in evening primrose nd borge seed oils. 9-18:1 n-9 12 desturse 9,12-18:2 n-6 6 desturse 6,9,12-18:3 n-6 In this instnce, the double in position 6 is inserted fter those in positions 9 nd 12. Biosynthesis of the (n-6) Fmily of Polyunsturted Ftty Acids In niml tissues, dditionl double bonds cn only be inserted between n existing double bond nd the crboxyl group. The linoleic cid, which is the primry precursor molecule for the (n-6) fmily of ftty cids, must come from the diet. Biosynthesis of polyunsturted ftty cids requires sequence of chin elongtion nd desturtion steps, s illustrted below, nd the vrious enzymes require the cyl-coenzyme A esters s substrtes not intct lipids (unlike plnts). The liver is the min orgn involved in the process. linoleic 9,12-18:2 (from the diet) 6-desturse γ-linolenic 6,9,12-18:3 elongtion dihomo-γ-linolenic 8,11,14-20:3 prostglndin PG 1 rchidonic 5-desturse 5,8,11,14-20:4 elongtion prostglndin PG 2 nd other eicosnoids 7,10,13,16-22:4 elongtion 9,12,15,18-24:4 6-desturse 6,9,12,15,18-24:5 retro-conversion 4,7,10,13,16-22:5 W.W. Christie 6

7 Ftty cids: methylene-interrupted double bonds - structures, occurrence nd biochemistry The first step is believed to be rte limiting nd involves desturtion with the introduction of double bond in position 6 to form γ-linolenic cid. Chin elongtion by two-crbon unit gives 20:3(n-6), which is converted to rchidonic cid by 5 desturse. This is the min end-product of the process. However, two further chin-elongtion steps yield 24:4(n-6), which cn be further desturted by 6 desturse to 24:5(n-6). All the enzymes to this stge re locted in the endoplsmic reticulum of the cell, but the lst ftty cid (24:5(n-6) must be trnsferred to the peroxisomes for retro-conversion (β-oxidtion) to 22:5(n-6). The mrine prsitic protozoon Perkinus mrinus (nd t lest three other unrelted unicellulr orgnisms) synthesises rchidonic cid by n lterntive pthwy in which elongtion of linoleic to 11,14-eicosdienoic cid is followed by sequentil desturtion by 8 nd 5 desturses. Biosynthesis of the (n-3) Fmily of Polyunsturted Ftty Acids Agin, the α-linoleic cid, which is the primry precursor molecule for the (n-3) fmily of ftty cids in niml tissues, must come from the diet. The min pthwy to the formtion of docoshexenoic cid (22:6(n-3)) requires sequence of chin elongtion nd desturtion steps ( 5 nd 6 desturses), s illustrted below, with cyl-coenzyme A esters s substrtes. Thus, α-linoleic cid is sequentilly elongted nd desturted, with double bonds being inserted between existing double bonds nd the crboxyl group, s fr s 24:6(n-3). α-linolenic 9,12,15-18:3 (from the diet) 6-desturse steridonic 6,9,12,15-18:4 elongtion 5-desturse 8,11,14,17-20:4 EPA 5,8,11,14,17-20:5 elongtion prostglndin PG 3 7,10,13,16,19-22:5 elongtion 4-desturse (micro-lge) 4,7,10,13,16,19-22:6 DHA 9,12,15,18,21-24:5 6-desturse 6,9,12,15,18,21-24:6 EPA = eicospentenoic DHA = docoshexenoic retro-conversion DHA 4,7,10,13,16,19-22:6 W.W. Christie 7

8 Ftty cids: methylene-interrupted double bonds - structures, occurrence nd biochemistry The finl steps of wht hs been termed the Sprecher pthwy involve retro-conversion, i.e. removl of the first two crbon toms by process of β-oxidtion, nd tke plce in the peroxisomes of the cell (s in the cse of the (n-6) fmily of ftty cids). All the vrious intermedites my be found in tissues, especilly those of fish, but eicospentenoic (20:5(n-3)), docospentenoic (22:5(n-3)) nd docoshexenoic (22:6(n-3)) cids tend to be by fr the most bundnt. In humn tissues, the rtes of conversion of α-linoleic cid to longer-chin metbolites is very low, suggesting tht high proportion of the ltter must come from the diet (met, eggs nd fish) in norml circumstnces. 4, 5 nd 8 Desturses hve been found in certin micro-lge of mrine origin (e.g. Pvlov slin), suggesting tht more direct route my exist in these orgnisms, i.e. vi desturtion of 22:5(n-3). With cetyl-coa s the primry precursor, the synthesis of 22:6(n-3) by the route described bove involves pproximtely 30 distinct enzymes nd 70 rections. However, n entirely different nd much simpler pthwy ctlysed by distinct polyketide synthse hs been found in mrine microbes. The conventionl view of polyketides is of secondry metbolites consisting of multiple building blocks of ketide groups ( CH 2 CO ), which re synthesised by polyketide synthse. This is n enzyme system similr to the ftty cid synthse in bcteri in tht it uses cyl crrier protein s covlent ttchment for chin synthesis nd proceeds in itertive cycles. However, the double bonds re introduced during the process of ftty cid synthesis in contrst to the elongtion-desturtion pthwy. Much remins to be lerned of this process in reltion to DHA synthesis, but it is believed tht s the chin elongtes the ketones groups re reduced to hydroxyls, nd this is followed by dehydrtion rections to introduce the double bonds. Thus, erobic desturtion is not required for introducing double bonds into the existing cyl chin, nd it is sometimes termed n nerobic pthwy, lthough it cn occur under erobic conditions. In contrst to higher plnts nd mmmls, the nemtode Cenorhbditis elegns possesses ll of the enzymes required for the synthesis of 20:4(n-6) nd 20:5(n-3) ftty cids de novo, fets tht cn lso be ccomplished by the fungus, Mortierell lpin, nd some mosses nd red lge. Essentil Ftty Acids As discussed briefly bove, linoleic nd linolenic cids cnnot be synthesised in niml tissues nd must be obtined from the diet, i.e. ultimtely from plnts. There is n bsolute requirement for these essentil ftty cids for growth, reproduction nd good helth. Young nimls deprived of these ftty cids in the diet rpidly disply the effects, including diminished growth, liver nd kidney dmge, nd dermtitis; these eventully result in deth. A key biochemicl prmeter is the triene-tetrene rtio, i.e. the rtio of 20:3(n-9) to 20:4(n-6) ftty cids in plsm; levels greter thn 0.4 reflect essentil ftty cid deficiency. It tkes longer for the effects to become pprent in older nimls, which my hve substntil stores of essentil ftty cids in their body fts, but symptoms will pper eventully. The effects of essentil ftty cid deficiency hve been seen in humn infnts, on dults on prenterl nutrition or with certin genetic disorders. The bsolute requirements re dependent on number of fctors, including species nd sex, but re usully considered to be 1-2% for linolete, nd somewht less for linolente. In contrst, the requirement for α-linolente in fish is higher thn for linolete. For some yers it ws believed tht cts lcked Delt-6 desturse nd hd n bsolute requirement for rchidonic cid especilly in their diet, i.e. they were obligte crnivores, but this now ppers not to be the cse. Linolete nd linolente my in fct be less importnt thn their longer-chin metbolites in niml biology. The functions of rchidonic, eicospentenoic nd docoshexenoic cids tht mke them essentil re only prtly understood. They re signlling molecules nd re involved in the regultion of gene expression. They re precursors of eicosnoids, including prostglndins W.W. Christie 8

9 Ftty cids: methylene-interrupted double bonds - structures, occurrence nd biochemistry (PG 1, PG 2 nd PG 3 series), thromboxnes, leukotrienes, nd lipoxins, which hve vriety of importnt biologicl properties. In ddition, these polyunsturted ftty cids confer distinctive ttributes on the complex lipids tht my be required for their function in membrnes. Although the ctul requirement for polyunsturted ftty cids is reltively low, generl nutritionl dvice for the humn diet until reltively recently ws tht they should comprise substntil prt of the dily intke. Now it is recognized tht the propensity of such ftty cids for oxidtion cn led to potentilly hrmful levels of hydroperoxides in tissues. Higher reltive proportions of monoenes re now recommended. Detiled discussion of this topic is not possible here. Recommended Reding o Brsh, A.R. Archidonic cid s bioctive molecule. J. Clin Invest., 107, (2001). o Cunnne,S.C. Problems with essentil ftty cids: time for new prdigm? Prog. Lipid Res., 42, (2003). o Gunstone, F.D., Hrwood, J.L. nd Pdley, F.B. (Editors). The Lipid Hndbook (2 nd Edition). Chpmn & Hll, London) (1994). o Gurr, M.I., Hrwood, J.L. nd Fryn, K. Lipid Biochemistry (5 th Edition). (Blckwells, London) (2002). o Holmn, R.T. (Editor). Progress in Lipid Reserch, Volumes 9 (1971) nd 25 (1986). - Severl chpters. o Nkmur, M.T. nd Nr, T.Y. Essentil ftty cid synthesis nd its regultion in mmmls. Prostglndins, Leukotrienes Essentil Ftty Acids, 68, (2003). o Poulos, A. Very long chin ftty cids in higher nimls - review. Lipids, 30, 1-14 (1995). o Qiu, X. Biosynthesis of docoshexenoic cid (DHA, 22:6-4,7,10,13,16,19): two distinct pthwys. Prostglndins, Leukotrienes Essentil Ftty Acids, 68, (2003). o SnGiovnn, J.P. nd Chew, E.Y. The role of omeg-3 long-chin polyunsturted ftty cids in helth nd disese of the retin. Prog. Retinl Eye Res., 24, (2005). o Vnce, D.E. nd Vnce, J. (Editors). Biochemistry of Lipids, Lipoproteins nd Membrnes (4 th Edition). (Elsevier, Amsterdm) (2002) Severl chpters. o Wllis, J.G., Wtts, J.L. nd Browse, J. Polyunsturted ftty cid synthesis: wht will they think of next? Trends Biochem. Sci., 27, (2002). o Wssll, S.R. nd Stillwell, W. Docoshexenoic cid domins: the ultimte non-rft membrne domin. Chem. Phys. Lipids, 153, (2008). W.W. Christie Scottish Crop Reserch Institute (nd MRS Lipid Anlysis Unit), Invergowrie, Dundee (DD2 5DA), Scotlnd Lst updted: W.W. Christie 9