Add time:08/02/2019         Source:sciencedirect.com

[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 Km value for NADH was approx. five times larger than the Km value for NADPH. It is inhibited by methimazole and not affected by CO. It is not induced by TTA.

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