PHYTANIC ACID ALPHA-OXIDATION IN RAT-LIVER MITOCHONDRIA

被引:9
|
作者
PAHAN, K [1 ]
GULATI, S [1 ]
SINGH, I [1 ]
机构
[1] MED UNIV S CAROLINA,DEPT PEDIAT,CHARLESTON,SC 29425
来源
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS | 1994年 / 1201卷 / 03期
关键词
MITOCHONDRION; PHYTANIC ACID OXIDATION; CIPROFIBRATE; CYTOCHROME P-450; (RAT LIVER);
D O I
10.1016/0304-4165(94)90081-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The alpha-oxidation of phytanic acid in rat liver is a mitochondrial function. The inhibition of phytanic acid oxidation activity by inhibitors of acyl-CoA ligases (Naproxen and Triacsin C) and that of carnitine acyltransferase I (2-(5-(4-chlorophenyl)pentyl)oxirane-2 carboxylic acid (POCPA) and 2-bromopalmitate) and increase in phytanic acid oxidation activity by the addition of exogenous carnitine and CoA to purified mitochondria suggests that phytanoyl-CoA ligase and carnitine acyltransferase I are essential for the activation and transport of phytanic acid across the mitochondrial membrane. This was further supported by the fact that activation of phytanic acid to phytanoyl-CoA was required only in intact mitochondria but not in mitochondria permealized with digitonin. DesulfoCoA, Naproxen and POCA treatment resulted in a significant decrease in phytanic acid oxidation in intact mitochondria but not in digitonin permealized mitochondria. These results show that alpha-oxidation of phytanic acid to pristanic acid, in contrast to beta-oxidation of fatty acids, requires free fatty acid as substrate. The inhibition of alpha-oxidation (similar to 90%) of phytanic acid by different cytochrome P-450 enzyme inhibitors indicated that alpha-oxidation of phytanic acid is mediated through cytochrome P-450 containing enzyme system. Similar to the omega-hydroxylation system in endoplasmic reticulum, alpha-hydroxylation and the subsequent cr-oxidation of phytanic acid in mitochondria is induced by ciprofibrate, a hypolipidemic drug.
引用
收藏
页码:491 / 497
页数:7
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