MICROSOMAL OXIDATION OF DODECYLTHIOACETIC ACID (A 3-THIA FATTY-ACID) IN RAT-LIVER

被引：33

作者：

HVATTUM, E ^{[1
]}

BERGSETH, S ^{[1
]}

PEDERSEN, CN ^{[1
]}

BREMER, J ^{[1
]}

AARSLAND, A ^{[1
]}

BERGE, RK ^{[1
]}

机构：

[1] UNIV BERGEN,CLIN BIOCHEM LAB,N-5014 BERGEN,NORWAY

来源：

BIOCHEMICAL PHARMACOLOGY | 1991年 / 41卷 / 6-7期

关键词：

D O I：

10.1016/0006-2952(91)90200-O

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

[1-C-14]Dodecylthioacetic acid (DTA), a 3-thia fatty acid, is omega (omega-1)-hydroxylated and sulfur oxygenated at about equal rates in rats liver microsomes. In prolonged incubations DTA is converted to omega-hydroxydodecylsulfoxyacetic acid. omega-Hydroxylation of DTA is catalysed by cytochrome P450IVA1 (or a very closely related isoenzyme in the same gene family), the fatty acid omega-hydroxylating enzyme. It is absolutely dependent on NADPH and inhibited by CO, and lauric acid is a competing substrate. omega-Hydroxylation of DTA is increased by feeding tetradecylthioacetic acid (TTA), a 3-thia fatty acid, for 4 days to rats. omega-Hydroxylation of [1-C-14]lauric acid is also induced by TTA and other 3-thia carboxylic acids. A close relationship was observed between induction of microsomal omega-hydroxylation of fatty acid and palmitoyl-CoA hydrolase activity. DTA is omega-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.

引用

页码：945 / 953

页数：9

共 29 条

[11] CYTOCHROME-P-450 INDUCTION BY CLOFIBRATE - PURIFICATION AND PROPERTIES OF A HEPATIC CYTOCHROME-P-450 RELATIVELY SPECIFIC FOR THE 12-HYDROXYLATION AND 11-HYDROXYLATION OF DODECANOIC ACID (LAURIC-ACID) [J].