oleoyl-coenzyme-a and lysophosphatidylethanolamine

delta 9-Tetrahydrocannabinol (THC) and merthiolate have been utilized as lysophospholipid acyltransferase inhibitors in metabolic studies. However, their effects on acyltransferases other than lysophosphatidylcholine:acyl-CoA acyltransferase (LPCAT) are not known. We have therefore investigated the effectiveness of THC and merthiolate in inhibiting the acylation of lysophosphatidylcholine, lysophosphatidylethanolamine, lysophosphatidylserine, lysophosphatidylinositol (LPI) and lysophosphatidic acid (LPA) in guinea pig liver microsomes using oleoyl-CoA and arachidonoyl-CoA as acyl donors. THC inhibited LPCAT and lysophosphatidylethanolamine:acyl-CoA acyltransferase (LPEAT) by 40-50%, but had no effect or only slightly increased the activities of the other acyltransferases when assayed with oleoyl-CoA as the acyl donor. The results obtained with arachidonoyl-CoA were similar to those with oleoyl-CoA, with the exception of a 40% inhibition of lysophosphatidylserine:acyl-CoA acyltransferase (LPSAT) at concentrations of 50 microM or higher. At similar concentrations, merthiolate was more effective than THC in inhibiting the acyltransferases examined. Selective effects on the acyltransferases were observed at low concentrations of merthiolate (20 microM or less). Thus, LPCAT was most susceptible, followed by LPI acyltransferases, LPSAT, LPEAT and lysophosphatidic acid:acyl-CoA acyltransferases (LPAAT). The presence of LPA did not affect the inhibition of LPCAT by merthiolate. Thus the resilience of LPAAT to merthiolate inhibition was not due to chelation of the compound by the acidic lysolipid. Thiol reagents including N-ethyl-maleiamide, 5,5'-dithio-bis-nitrobenzoic acid, iodoacetate, beta-mercaptoethanol and dithiothreitol had little or no effect on the acyltransferases relative to equimolar concentrations of merthiolate.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acyl Coenzyme A; Acyltransferases; Animals; Dronabinol; Guinea Pigs; Lysophosphatidylcholines; Lysophospholipids; Microsomes, Liver; Substrate Specificity; Sulfhydryl Reagents; Thimerosal

1. Alveolar type II cells from adult rat lung have the enzymic capability to acylate 1-palmitoyl-lysophosphatidyl-glycerol, using palmitoyl-CoA to form dipalmitoylphosphatidylglycerol. 2. On a protein basis the acylation of 1-palmitoyl-lysophosphatidylglycerol is at least 2-fold more active in sonicated type II cells than in whole lung homogenates. 3. Both type II cells and whole lung homogenates show higher activity towards palmitoyl-CoA than towards oleoyl-CoA for acylation of 1-palmitoyl-lysophosphatidylglycerol. 4. Both in type II cells and in whole lung homogenates the rates of acylation of 1-palmitoyl-lysophosphatidylglycerol and 1-palmitoyl-lysophosphatidylcholine with palmitate are of the same order of magnitude, while the rate of acylation of 1-palmitoyl-lysophosphatidylethanolamine is much lower.

Topics: Acyl Coenzyme A; Acylation; Acyltransferases; Animals; Lysophosphatidylcholines; Lysophospholipids; Male; Oleic Acids; Palmitoyl Coenzyme A; Phosphatidylethanolamines; Phosphatidylglycerols; Pulmonary Alveoli; Pulmonary Surfactants; Rats; Rats, Inbred Strains