Pahan K, Gulati S, Singh I
Department of Pediatrics, Medical University of South Carolina, Charleston 29425.
Biochim Biophys Acta. 1994 Dec 15;1201(3):491-7. doi: 10.1016/0304-4165(94)90081-7.
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 (POCA) 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 (approximately 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 alpha-oxidation of phytanic acid in mitochondria is induced by ciprofibrate, a hypolipidemic drug.
植烷酸在大鼠肝脏中的α-氧化是一种线粒体功能。酰基辅酶A连接酶抑制剂（萘普生和三辛菌素C）以及肉碱酰基转移酶I抑制剂（2-(5-(4-氯苯基)戊基)环氧乙烷-2-羧酸（POCA）和2-溴棕榈酸酯）对植烷酸氧化活性的抑制，以及向纯化的线粒体中添加外源性肉碱和辅酶A后植烷酸氧化活性的增加，表明植烷酰辅酶A连接酶和肉碱酰基转移酶I对于植烷酸穿过线粒体膜的激活和转运至关重要。这一观点进一步得到以下事实的支持：只有完整的线粒体需要将植烷酸激活为植烷酰辅酶A，而用洋地黄皂苷通透处理的线粒体则不需要。去硫辅酶A、萘普生和POCA处理导致完整线粒体中的植烷酸氧化显著降低，但洋地黄皂苷通透处理的线粒体中则没有。这些结果表明，与脂肪酸的β-氧化不同，植烷酸向降植烷酸的α-氧化需要游离脂肪酸作为底物。不同的细胞色素P-450酶抑制剂对植烷酸α-氧化的抑制（约90%）表明，植烷酸的α-氧化是通过含细胞色素P-450的酶系统介导的。与内质网中的ω-羟基化系统类似，降血脂药物环丙贝特可诱导线粒体中植烷酸的α-羟基化及随后的α-氧化。
