Lipids and biomembranes

Transcription

1 Lipids and biomembranes Tomáš Kučera Department of Medical hemistry and linical Biochemistry 2nd Faculty of Medicine, harles University in Prague and Motol University Hospital MMXVIII

2 Lipids Definition non-polar (hydrophobic) compounds of biological origin, soluble in organic solvents (in water limitedly or not at all) Major roles structural components of biological membranes energy storage (triacylglycerols) thermal (and electric) insulators protective layers against infection, clashes and dessication vitamins and hormones and their precursors bile acids lipid solubilization

3 Fatty acids FA important components of most other lipids a hydrocarbon chain (4 36 ) with a carboxyl at one end amphipathic non-polar end polar end a 16- fatty acid: 3 ( 2 ) 14 saturated or unsaturated free rotation around bonds no rotation around bonds esterified or free salts with alkali metals soaps

4 Fatty acids of various length SFA (< 6 ) MFA (6 12 ) LFA (12 22 ) (14 20) VLFA (> 22 ) lower (< 10 ) higher (> 12 )

5 Fatty acids Example: octadeca-9,12-dienoic acid γ 4 β 3 α 2 1 H 18- FA with two cis double bonds in positions 9 and 12 linoleic acid (9,12-octadecadienoic) n ω 18:2 Δ 9,12 = 18:2 ω6 = 18:2 n 6 = = cis,cis-18:2 Δ 9,12 = cis,cis-18:2 ω6 = cis,cis-18:2 n 6 = = all-cis-18:2 Δ 9,12 = all-cis-18:2 ω6 = all-cis-18:2 n 6 = = cis,cis-18:2(9,12) = all-cis-18:2(9,12) = 18:2(9c,12c)

6 Fatty acids usually linear hydrocarbon chain an even number of carbon atoms double bonds in cis configuration a rigid kink at each bond H stearic acid acid 18:1(11c) oleic acid linoleic acid FA melting points decrease with shorter chains unsaturation vicinity of the first to the carboxyl

7 Some common fatty acids ommon name Symbol Systematic name m.p. ( ) Formula Saturated lauric 12:0 dodecanoic 44.2 myristic 14:0 tetradecanoic 52.0 palmitic 16:0 hexadecanoic 63.1 stearic 18:0 octadecanoic 69.6 arach(id)ic 20:0 eicosanoic 75.4 behenic 22:0 docosanoic 81.0 lignoceric 24:0 tetracosanoic 84.2 With one double bond (MUFA) palmitoleic 16:1 ω7 hexadec-9-enoic 0.5 oleic 18:1 ω9 oktadec-9-enoic 13.4 erucic 22:1 ω9 docosa-13-enoic nervonic 24:1 ω9 tetracosa-15-enoic 39.0 With two double bonds linoleic 18:2 ω6 octadeca-9,12-dienoic 9.0 With three double bonds ( PUFA ) α-linolenic 18:3 ω3 octadeca-9,12,15-trienoic 17.0 γ-linolenic 18:3 ω6 octadeca-6,9,12-trienoic With four double bonds arachidonic 20:4 ω6 eicosa-5,8,11,14-tetraenoic 49.5 With five double bonds timnodonic (EPA) 20:5 ω3 eicosa-5,8,11,14,17-pentaenoic 54.0 clupanodonic (DPA) 22:5 ω3 docosa-7,10,13,16,19-pentaenoic With six double bonds cervonic (DHA) 22:6 ω3 docosa-4,7,10,13,16,19-hexaenoic essential: linoleic and α-linolenic

8 Some less common fatty acids ommon name Symbol Systematic name ω Formula With odd-numbered chain 13:0 tridecanoic 15:0 pentadecanoic 17:0 heptadecanoic 17:1(9c) cis-heptadec-9-enoic 8 Branched (MUFA) iso-tridecanoic iso-13:0 11-methyldodecanoic 7 iso-tetradecanoic iso-14:0 12-methyltridecanoic iso-pentadecanoic iso-15:0 13-methyltetradecanoic iso-hexadecanoic iso-16:0 14-methylpentadecanoic iso-heptadecanoic iso-17:0 15-methylhexadecanoic anteiso-tridecanoic anteiso-13:0 10-methyldodecanoic anteiso-pentadecanoic anteiso-15:0 12-methyltetradecanoic anteiso-heptadecanoic anteiso-17:0 14-methylhexadecanoic phytanic 3,7,11,15-tetramethylhexadecanoic pristanic 2,6,10,14-tetramethylpentadecanoic onjugated linoleic acid (LA) 18:2(9c,11t) 9-cis,11-trans-octadeca-9,11-dienoic 8 18:2(10t,12c) 10-trans,12-cis-octadeca-10,12-dienoic 7 With a triple bond tariric 18:1(6a) octadec-6-ynoic

9 Some really exotic fatty acids e.g. haliclonyne (47 FA): 14-oxo-4,5,6,28,33,37,42,45- octahydroxy-trans-26,trans-43-dien-2,31,34,46-tetraynheptatetracontanoic acid H H H H ( 2 ) 7 ( 2 ) 10 ( 2 ) 4 H H H H H cyclopropane to cyclohexane ring epoxy-, cyclic peroxides, SH, disulfides fatty alcohols similar diversity H H H

10 verview of lipids Simple lipids esters of FA with alcohols fats & oils (acylglycerols, glycerides): alcohol = glycerol waxes: alcohol = long-chain (mono)alcohol omplex lipids esters FA+alcohols + other items phospholipids FA + glycerol + phosphate + something glycolipids contain sugars glycoacylglycerols FA + glycerol + sugar glycosphingolipids FA + sphingosine + sugar (+ sialic acid) sphingolipids contain ceramide (amide FA+sphingosine) sphingomyelins ceramide + phosphocholine glycosphingolipids see above Derived lipids other biological hydrophobic substances, e.g. steroids, eicosanoids, docosanoids, carotenoids and other terpenoids, lipophilic vitamins

11 Simple lipids Esters of fatty acids with alcohols Waxes (cerides) the alcohol is long, monovalent fatty the most fatty of the lipids in animals final metabolites usually a protective function plant cuticule lanolin beeswax beeswax main component 15 H H 61 myricyl palmitate triacontyl hexadecanoate carnauba wax main component 25 H H 61 myricyl cerotate triacontyl hexacosanoate

12 Simple lipids H 2 H H 2 H H H glycerol H R FA H 2 R 1 H R 2 H 2 R 3 triacylglycerol Triacylglycerols (triglycerides, neutral fats and oils) the most abundant dietary lipids energy storage reduced compact (dehydrated) protective layers glycerol backbone + 3 esterified FA most are mixed

13 omplex lipids sphingolipids, glycerolipids phospholipids glycerophospholipids (PE, PS, P, PG, DPG, PI; plasmalogens) sphingomyelins glycolipids glycoacylglycerols glycosphingolipids cerebrosides gangliosides all complex lipids include non-polar FA chains ( tails ) include polar region (glycerol, FA carbonyls, usually P i, the polar head group they are amphipathic

14 Glycerophospholipids (phosphoglycerides) common constituents of biological membranes glycerol backbone hydroxyls at 1 & 2 esterified with fatty acids 3 esterified with P i Phosphatidic acids R 2 H 2 H 2 P R 1 the simplest phospholipids only small amounts in the membranes only intermediates in the synthesis of triacylglycerols and glycerophospholipids

15 Glycerophospholipids H 2 R 1 R 2 H 2 P X polar head usually, P i is further esterified to H of a polar head group (signed X in the figure) e.g. serine, choline, ethanolamine, glycerol, or inositol The 2 fatty acids tend to be non-identical. amphipathic (complex polar region)

16 Glycerophospholipids Phosphatidylinositols (PI) membrane lipids R 2 H 2 H 2 P R 1 cellular signaling molecules H H H H H Phosphatidylcholines (lecithins, P) R 2 H 2 H 2 P R N common membrane lipids

17 Glycerophospholipids Plasmalogens H 2 R 1 R 2 H 2 P X glycerol enol-ether phospholipids in mammals R 1 (the fatty alcohol) usually 16:0, 18:0, or 18:1 R 2 usually PUFA X=usually ethanolamine or choline (or serine) brain and muscles PAF (platelet activating factor) platelet aggregation R 1 = 16:0, R 2 = acetyl, X= cholin R 2 acetyl higher solubility

18 Sphingolipids derivatives of the amino alcohol sphingosine H H H H H 2 H H 2 H N H 2 NH H H ( 2 ) 12 (10 14) R ( 2 ) 12 3 sphingosine 3 ceramide amides of sphingosine with FA = ceramides other sphingolipids include a polar head group, esterified to the terminal H of the sphingosine.

19 Sphingolipids Sphingomyelins (phosphosphingolipids) 3 H 3 N P 3 H H 2 H NH H R ( 2 ) 12 3 ceramides with the phosphocholine or phosphoethanolamine head group common constituent of plasma membranes in brain and nerve tissue

20 Glycosphingolipids erebrosides β,d-glc (or β,d-gal) H 2 H NH H R H ( 2 ) 12 3 ceramides with a monosaccharide such as glucose or galactose as polar head group Gangliosides H 3 NH H H 2 H H H H N-acetylneuraminic acid ceramides with a polar head group that is a complex oligosaccharide, containing a sialic acid common in the outer layer of the plasma membrane sugar chains extend outwards

21 Glycolipids glycoacylglycerols R 2 R 2 H 2 H 2 H 2 H 2 R 1 β,d-gal-1,6-α,d-gal H R 1 H mono- and digalactosyl diacyl glycerols sulfoquinovosyl diacyl glycerols 3 S H 2 H important constituents of plant membranes thylakoid membrane

22 Derived lipids Isoprenoids isoprene geranene farnesene geranylgeranene phytene squalene phytoene monoterpenes (menthol, limonene, camphor, pinene, geraniol) sesquiterpenes (humulene, zingiberene) diterpenes (geranylgeraniol, taxadiene, kahweol, cafestol, phytol (chains of chlorophyll, vitamins E and K) triterpenes (steroids) tetraterpenes (carotenoids vitamin A)

23 Steroids cholesterol H 21 H H 3 important constituent of cell membranes a rigid ring system and a short branched hydrocarbon tail hydrophobic amphipathy (weak) conferred by the H precursor of D vitamin bile acids sex hormones adrenocortical hormones

24 Biological membranes lipids in polar environments aggregation to complexes in which polar regions are in contact with water and hydrophobic regions away from water. possible molecular arrangements: various micelle structures spherical micelles stable form of FA a bilayer stable form for amphipathic lipids such as phospholipids zdroj

25 Biological membranes phospholipid bilayer with proteins inserted in it or bound to the surface zdroj Berg, J. M., Tymoczko, Gatto, G. J. Jr., J. L., Stryer, L.: Biochemistry, W. H. Freeman and ompany, 2012 (8th edition) integral proteins embedded in the bilayer trans-membrane peripheral proteins bound to the surface of the membrane many of the proteins and lipids carry oligosaccharide chains

26 Biological membrane fluidity the interior of a lipid bilayer is normally highly fluid. liquid (fluid) state hydrocarbon chains disordered and in constant motion (higher temperatures) crystalline state fatty acid tails are fully extended, packing is highly ordered (lower temperatures) Voet, D., Voet, J. G.: Biochemistry, John Wiley & Sons, Inc., 2011 (4th edition) Stryer, L.: Biochemistry, W. H. Freeman and ompany, 1981 (2nd edition)

27 Biological membrane fluidity FA types see above holesterol inserts into bilayer membranes hydroxyl group oriented out polar environment hydrogen bonds with polar heads of membrane lipids hydrophobic ring system adjacent to FA chains of membrane lipids hydrophobic interactions rather rigid molecule interactions with membrane lipid hydrocarbon chains decreases the membrane fluidity H H zdroj

28 Biological membrane assymmetry Stryer, L.: Biochemistry, W. H. Freeman and ompany, 1981 (2nd edition) lateral mobility of a lipid is high transversal mobility (flip-flop) of lipids is very low of proteins has never been observed Stryer, L.: Biochemistry, W. H. Freeman and ompany, 1981 (2nd edition)

29 Biological membrane assymmetry the two leaflets are different assymmetry in lipid composition protein composition and orientation saccharides of glycoproteins and glycolipides function

30 Membrane microdomains lipid rafts more sphingolipids (by 50 %) cholesterol (3 5 ) saturated FA less phosphatidylcholine ( equal choline) function intercellular signalling, endocytosis, interaction vith viruses

31 The End konec the end Thank you for your attention!

32 Glycerophospholipids (phosphoglycerides) H 2 R 1 R 2 H 2 P

33 Glycerophospholipids H 2 R 1 R 2 H 2 P X

34 Glycerophospholipids R 2 H 2 R 1 mem cellu H 2 P H H H H H

35 Glycerophospholipids H 2 R 1 R 2 3 H 2 P 2 2 N + 3 3

36 cerol enol-ether pho Glycerophospholipids H 2 R 1 R 2 H 2 P X

37 Sphingolipids H H H H 2 H H 2 N H 2 H ( 2 ) 12 (10 14) 3 sphingosine c

38 Sphingolipids H H H 2 H NH R H ( 2 ) 12 3 ceramide

39 Sphingolipids 3 H 3 N P 3 H H 2 H NH R H ( 2 ) 12 3

40 Glycosphingolipids β,d-glc (or β,d-gal) H 2 H NH H R H ( 2 ) 12 3

41 Gangliosides Glycosphingolipids H 3 NH H H 2 H H H H N-acetylneuraminic acid

42 lycoacylglycerols Glycolipids H 2 R 1 R 2 H 2 β,d-gal-1,6-α,d-gal H 2 R 1

43 Glycolipids H 2 R 1 su R 2 H 2 H H H 3 S H 2

44 Derived lipids isoprene 5 geranene 10 farnesene 15 geranylgeranene 20 phytene 20 squalene 30 phytoene 40 monoterpenes (menthol, limonene, camphor geraniol) sesquiterpenes (humulene, zingiberene) diterpenes (geranylgeraniol, taxadiene, kahw

45 Steroids cholesterol important constituent of c H H H

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