COENZYME A-DEPENDENT CLEAVAGE OF MEMBRANE PHOSPHOLIPIDS IN SEVERAL RAT-TISSUES - ATP-INDEPENDENT ACYL-COA SYNTHESIS AND THE GENERATION OF LYSOPHOSPHOLIPIDS

Substantial amounts of acyl-CoA were formed when microsomes from sever al rat tissues were incubated with varying concentrations of free CoA and bovine serum albumin even in the absence of ATP and Mg2+. For inst ance, 86 nmol of acyl-CoA was produced when microsomes (5 mg protein) were incubated with 300 mu M CoA for 30 min. It was calculated that 1. 8% of total fatty acyl residues were converted to acyl-CoA. during the incubation. No appreciable amount of acyl-CoA was formed from free fa tty acid or from boiled microsomes under the same experimental conditi ons. These observations indicate that acyl-CoA is formed from microsom al lipids by an enzyme activity distinct from previously known long-ch ain fatty acyl-CoA synthetase. The apparent K-m value for CoA and V-ma x were 180 mu M and 20 nmol/30 min per mg protein, respectively. We fo und that several species of acyl-CoA such as arachidonoyl-CoA were pre ferentially synthesized through the reaction and that several types of phospholipids actually act as acyl donors in the formation of acyl-Co A. Phosphatidylinositol and phosphatidylcholine appear to be preferred substrates. We confirmed that lysophosphatidylinositol and lysophosph atidylcholine were generated along with the formation of acyl-CoA. It seems very likely that CoA-mediated cleavage of phospholipids/ATP-inde pendent acyl-CoA synthesis is implicated in the metabolism of certain types of fatty acyl residues of membranous phospholipids in mammalian cells.