Microsomal oxidation of dodecylthioacetic acid (a 3-thia fatty acid) in rat liver

[1- 14C]odecylthioacetic acid (DTA), a 3-thia fatty acid, is ω (ω-1)-hydroxylated and sulfur oxygenated at about equal rates in rat liver microsomes. In prolonged incubations DTA is converted to (ω-hydroxydodecylsulfoxyacetic acid. ω-Hydroxylation of DTA is catalysed by cytochrome P450IVA1 (or a very closely related isoenzyme in the same gene family), the fatty acid ω- hydroxylating enzyme. It is absolutely dependent on NADPH and inhibited by CO, and lauric acid is a competing substrate. ω-Hydroxylation of DTA is increased by feeding tetradecylthioacetic acid (TTA), a 3-thia fatty acid, for 4 days to rats. ω-Hydroxylation of [1- 14C]lauric acid is also induced by TTA and other 3-thia carboxylic acids. A close relationship was observed between induction of microsomal ω-hydroxylation of fatty acid and palmitoyl-CoA hydrolase activity. DTA is ω-hydroxylated at about the same rate as the physiological substrate lauric acid. The sulfur oxygenation of DTA is catalysed by liver microsomal flavin-containing monooxygenase (FMO) (EC 1.14.13.8). It is dependent on either NADH or NADPH. The K m value for NADH was approx. five times larger than the K m value for NADPH. It is inhibited by methimazole and not affected by CO. It is not induced by TTA.