Formation of acylphosphatidylglycerol by a lysosomal phosphatidylcholine:bis(monoacylglycero)phosphate acyl transferase.
A delipidated soluble fraction prepared from a mitochondrial-lysosomal fraction of rabbit alveolar macrophages that catalyzes transacylation of lysophosphatidylglycerol to form bis(monoacylglycero)phosphate was also found to transfer oleic acid from [14C]dioleoyl phosphatidylcholine to form acylphosphatidylglycerol. The reaction was dependent on the presence of bis(monoacylglycero)phosphate and was maximal at a concentration of 44 microM when the ratio of fatty acid transferred to fatty acid released was 0.28. Addition of phosphatidylglycerol had only a small effect. Homogenates of rat liver also catalyzed the reaction and after subcellular fractionation the activity was localized to lysosomes. The lysosomal activity was solubilized by delipidation with butanol to give a preparation with a specific activity 2462 times that of the homogenate. Optimal activity of soluble preparations from both macrophages and liver was at pH 4.5, with little activity above 6.0. Release of free fatty acid was also stimulated under conditions of optimal acyl transfer. Both acyl transfer and release of fatty acid were inhibited by Ca2+, detergents, chlorpromazine, lysophosphatidylcholine, and oleic acid. When there was disproportional inhibition, acyl transfer was always more affected. These results suggest that sequential acylation of lysophosphatidylglycerol to form bis(monoacylglycero)phosphate and then acylphosphatidylglycerol constitute a mechanism in the lysosome for the transport and partition of fatty acids released by the lysosomal phospholipases.
Huterer
S J
SJ
Department of Medicine (Neurology), University of Toronto, Ont., Canada.
Wherrett
J R
JR
D000135:Acid Phosphatase / Q000378:metabolism; D000217:Acyltransferases; D000818:Animals; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008246:Lysophospholipids / Q000378:metabolism* / Q000494:pharmacology; D008247:Lysosomes / Q000201:enzymology*; D008264:Macrophages / Q000201:enzymology; D008297:Male; D050178:Monoglycerides; D010713:Phosphatidylcholines / Q000378:metabolism*; D010715:Phosphatidylglycerols / Q000096:biosynthesis*; D011650:Pulmonary Alveoli / Q000201:enzymology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012995:Solubility; D014166:Transferases / Q000378:metabolism*
D008246:Lysophospholipids; D050178:Monoglycerides; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; C012786:bis(monoacylglyceryl)phosphate; D014166:Transferases; D000217:Acyltransferases; C024365:bis(monoacylglycero)phosphate synthetase; D000135:Acid Phosphatase