Metabolic relationship between arachidonate activation and its transfer to lysophospholipids by brain microsomes

Evidence is presented to indicate a metabolic relationship between arachidonic acid activation and its transfer to lysophospholipds by brain microsomes. Thus, in the presence of 1-acylglycerophosphocholines or 1-acyl-glycerophosphoinositols, the activation of labeled arachidonate to its acyl-CoA was enhanced, and the acyl-CoA formed was, in turn, transferred to the lysophospholipids to form the respective diacyl-glycerophospholipids. The coupling effect seems to pertain mainly to the lysophospholipids which are good substrates of the acyltransferase. Other lyso-compounds were either not effective or inhibitory to the arachidonate activation process. The activation-transfer activity mediated by the fatty acid ligase and acyltransferase could be dissociated by Triton X-100, which apparently stimulated the acyl-CoA ligase activity but inhibited the acyltransferase. These results suggest that fatty acid ligase and acyltransferase are located in close proximity within the membrane domain. The existence of a close metabolic relationship between these two enzymic reactions is important for maintaining a dynamic equilibrium between the free fatty acids and the membrane phospholipids. The mechanism is also useful in regulating the cellular acyl-CoA and lysophospholipid metabolism, because both compounds have membrane perturbing properties when present in excessive quantity.