EFFECTS OF TETRADECYLTHIOPROPIONIC ACID AND TETRADECYLTHIOACRYLIC ACID ON RAT-LIVER LIPID-METABOLISM

Studies of effects of 4-thia-substituted fatty acid analogues on rat l iver lipid metabolism are described. With isolated hepatocytes tetrade cylthiopropionate was shown to divert [1-C-14]oleate from beta-oxidati on into esterification, the total amount of [1-C-14]oleate metabolized remaining unchanged. Tetradecylthiopropionyl-CoA was a good substrate for mitochondrial carnitine palmitoyltransferases I and II (EC 2.3.1. 21), acyl-CoA oxidase (EC 1.3.3.6), for the microsomal (but not mitoch ondrial) glycerophosphate acyltransferase (EC 2.3.1.15), and for long- chain acyl-CoA dehydrogenase (EC 1.3.99.3). In isolated hepatocytes, i ts 4-thia-trans-2-enoic derivative, tetradecylthioacrylate, inhibits b oth beta-oxidation of, and incorporation of, [1-C-14]oleate into lipid s. In rat liver mitochondria tetradecylthioacrylate inhibited beta-oxi dation. The degree of inhibition was not markedly increased by preincu bation with tetradecylthioacrylate. Tetradecylthioacrylyl-CoA was a po or substrate for carnitine palmitoyltransferase I, and inhibited carni tine palmitoyltransferase II: microsomal glycerophosphate acyltransfer ase and acyl-CoA oxidase. It is concluded that the inhibitory effects of tetradecylthiopropionyl-CoA are expressed intramitochondrially, whe reas primary sites of inhibition by tetradecylthioacrylyl-CoA are extr amitochondrial.