Harpers

METABOLISM OF ACYLGLYCEROLS & SPHINGOLIPIDS / 201ACYLTRANSFERASEAcyl-CoAFigure 24–5.(lecithin).OR 2 C O C HH 2 C OOH 2 C O C R 1PPhosphatidylcholineH 2 OCholinePHOSPHOLIPASE A 2R 2H 2 CH 2 CCOOHOH 2 C O C R 1HO C HH 2 C O P CholineLysophosphatidylcholine (lysolecithin)H 2 OLYSOPHOSPHOLIPASER 1 COOHH 2 C OHHO C HO P CholineGlycerylphosphocholineH 2 OGLYCERYLPHOSPHO-CHOLINE HYDROLASEH 2 C OHHO C H + CholineO Psn-Glycerol 3-phosphateMetabolism of phosphatidylcholinePHOSPHOLIPASE BOR 2 C O C HH 2 C OPHOSPHOLIPASE A 2H 2 C O C R 1PHOSPHOLIPASE A 1OOPO –OPHOSPHOLIPASE CPHOSPHOLIPASE DN-BASEFigure 24–6. Sites of the hydrolytic activity of phospholipaseson a phospholipid substrate.found in plasma, catalyzes the transfer of a fatty acidresidue from the 2 position of lecithin to cholesterol toform cholesteryl ester and lysolecithin and is consideredto be responsible for much of the cholesteryl ester inplasma lipoproteins. Long-chain saturated fatty acidsare found predominantly in the 1 position of phospholipids,whereas the polyunsaturated acids (eg, the precursorsof prostaglandins) are incorporated more intothe 2 position. The incorporation of fatty acids intolecithin occurs by complete synthesis of the phospholipid,by transacylation between cholesteryl ester andlysolecithin, and by direct acylation of lysolecithin byacyl-CoA. Thus, a continuous exchange of the fattyacids is possible, particularly with regard to introducingessential fatty acids into phospholipid molecules.ALL SPHINGOLIPIDS ARE FORMEDFROM CERAMIDECeramide is synthesized in the endoplasmic reticulumfrom the amino acid serine according to Figure 24–7.Ceramide is an important signaling molecule (secondmessenger) regulating pathways including apoptosis(processes leading to cell death), cell senescence, anddifferentiation, and opposes some of the actions of diacylglycerol.Sphingomyelins (Figure 14–11) are phospholipidsand are formed when ceramide reacts with phosphatidylcholineto form sphingomyelin plus diacylglycerol(Figure 24–8A). This occurs mainly in the Golgiapparatus and to a lesser extent in the plasma membrane.Glycosphingolipids Are a Combinationof Ceramide With One or MoreSugar ResiduesThe simplest glycosphingolipids (cerebrosides) aregalactosylceramide (GalCer) and glucosylceramide(GlcCer). GalCer is a major lipid of myelin, whereasGlcCer is the major glycosphingolipid of extraneuraltissues and a precursor of most of the more complexglycosphingolipids. Galactosylceramide (Figure 24–8B)is formed in a reaction between ceramide and UDPGal(formed by epimerization from UDPGlc—Figure20–6). Sulfogalactosylceramide and other sulfolipidssuch as the sulfo(galacto)-glycerolipids and thesteroid sulfates are formed after further reactions involving3′-phosphoadenosine-5′-phosphosulfate (PAPS;“active sulfate”). Gangliosides are synthesized fromceramide by the stepwise addition of activated sugars (eg,UDPGlc and UDPGal) and a sialic acid, usually N-acetylneuraminic acid (Figure 24–9). A large numberof gangliosides of increasing molecular weight may beformed. Most of the enzymes transferring sugars from