Harpers

200 / CHAPTER 24H 2 COHO CH 2 C O PAcyl-CoAACYL-TRANSFERASEOH 2 CO CH 2 C O POHNADPH+ H + NADP +H 2 C O (CH 2 ) 2 R 2H 2 C O (CH 2 ) 2 R 2O CHO C HSYNTHASE H 2 C O PREDUCTASE H 2 C O PO C R 1R 2HOOC R 1Dihydroxyacetonephosphate1-Acyldihydroxyacetonephosphate1-Alkyldihydroxyacetonephosphate1-Alkylglycerol 3-phosphateAcyl-CoA(CH 2 ) 2 R 2(CH 2 ) 2 R 2ACYL-TRANSFERASECDP-CMP EthanolamineP i H 2 OO H 2 C OO H 2 C OO H 2 C O (CH 2 ) 2 R 2R 3 C O C HR 3 C O C HR 3 C O C HH 2 C O P CH 2 CH 2 NH 2CDP-ETHANOLAMINE:ALKYLACYLGLYCEROLH 2 C OH PHOSPHOHYDROLASEH 2 C O P1-Alkyl-2-acylglycerolPHOSPHOETHANOLAMINETRANSFERASE3-phosphoethanolamine1-Alkyl-2-acylglycerol1-Alkyl-2-acylglycerol 3-phosphateCDP-cholineNADPH, O 2,DESATURASECDP-CHOLINE:Cyt b ALKYLACYLGLYCEROL5PHOSPHOCHOLINEAlkyl, diacyl glycerolsTRANSFERASER 3OCMPH 2 C O CH CH R 2O H 2 C O (CH 2 ) 2 R 2C O C HH 2 O R 3 COOHR 3 C O C HH 2 C O (CH 2 ) 2 R 2H 2 C O P (CH 2 ) 2 NH 2H 2 C O PHO C HPHOSPHOLIPASE A1-Alkenyl-2-acylglycerol2CholineH 2 C O P3-phosphoethanolamineplasmalogen1-Alkyl-2-acylglycerolCholine3-phosphocholine1-Alkyl-2-lysoglycerolAcetyl-CoA3-phosphocholineACETYLTRANSFERASE*OH 2 CO(CH 2 ) 2 R 2H 3 CCOCHH 2 COPCholine1-Alkyl-2-acetylglycerol 3-phosphocholinePAFFigure 24–4. Biosynthesis of ether lipids, including plasmalogens, and platelet-activating factor (PAF). In thede novo pathway for PAF synthesis, acetyl-CoA is incorporated at stage *, avoiding the last two steps in the pathwayshown here.Phospholipases Allow Degradation& Remodeling of PhosphoglycerolsAlthough phospholipids are actively degraded, eachportion of the molecule turns over at a different rate—eg, the turnover time of the phosphate group is differentfrom that of the 1-acyl group. This is due to thepresence of enzymes that allow partial degradation followedby resynthesis (Figure 24–5). Phospholipase A 2catalyzes the hydrolysis of glycerophospholipids to forma free fatty acid and lysophospholipid, which in turnmay be reacylated by acyl-CoA in the presence of anacyltransferase. Alternatively, lysophospholipid (eg, lysolecithin)is attacked by lysophospholipase, formingthe corresponding glyceryl phosphoryl base, which inturn may be split by a hydrolase liberating glycerol3-phosphate plus base. Phospholipases A 1 , A 2 , B, C,and D attack the bonds indicated in Figure 24–6.Phospholipase A 2 is found in pancreatic fluid andsnake venom as well as in many types of cells; phospholipaseC is one of the major toxins secreted by bacteria;and phospholipase D is known to be involved inmammalian signal transduction.Lysolecithin (lysophosphatidylcholine) may beformed by an alternative route that involves lecithin:cholesterol acyltransferase (LCAT). This enzyme,