Singh H, Beckman K, Poulos A
Department of Chemical Pathology, Women's and Children's Hospital, North Adelaide, Australia.
J Biol Chem. 1994 Apr 1;269(13):9514-20.
Fatty acid beta-oxidation was investigated in highly purified mitochondrial and peroxisomal preparations from rat liver. Under isotonic conditions, pristanic and homophytanic acid beta-oxidation in purified peroxisomes was severalfold greater compared to the oxidation in purified mitochondria. Branched chain fatty acid beta-oxidation in purified mitochondria was very low, and the oxidation was not stimulated by exogenous L-carnitine or L-malate. In contrast, stearic acid beta-oxidation by purified mitochondria depended upon exogenous L-carnitine, and the oxidation was stimulated by L-malate. Both mitochondrial and peroxisomal beta-oxidation of branched chain fatty acids was strongly inhibited by fatty acid-free bovine serum albumin, whereas stearic acid oxidation was either unaffected or slightly inhibited by bovine serum albumin. The results presented clearly indicate that branched chain fatty acids are mainly degraded in peroxisomes in rat liver. Branched chain fatty acids were efficiently converted to coenzyme A thioesters by purified mitochondria, peroxisomes, and microsomes. Although pristanic and phytanic acids were rapidly converted to pristanoyl-CoA and phytanoyl-CoA, respectively, they were not converted to carnitine esters by mitochondrial outer membranes. The results indicate that acyl-CoA synthetase and carnitine acyltransferase located at the mitochondrial outer membranes regulate entry of branched chain fatty acids into mitochondria. Mitochondrial carnitine acyltransferase I appears to be highly specific for straight chain fatty acids and restricts entry of branched chain fatty acids into mitochondria. Thus, branched chain fatty acids which cannot be transported across the mitochondrial membranes via the carnitine acyltransferase system are directed to peroxisomes for beta-oxidation. The results reported indicate that phytanic acid, the fatty acid which can be initially degraded by alpha-oxidation due to the presence of a beta-methyl group in the molecule, cannot be transported across the mitochondrial membranes. The data presented strongly suggest that phytanic acid alpha-oxidation occurs in organelles other than mitochondria and possibly in peroxisomes.
在来自大鼠肝脏的高度纯化的线粒体和过氧化物酶体制剂中研究了脂肪酸β-氧化。在等渗条件下，纯化的过氧化物酶体中降植烷酸和植烷酸β-氧化比纯化的线粒体中的氧化作用大几倍。纯化线粒体中支链脂肪酸β-氧化非常低，且该氧化作用不受外源性L-肉碱或L-苹果酸刺激。相反，纯化线粒体的硬脂酸β-氧化依赖于外源性L-肉碱，且该氧化作用受L-苹果酸刺激。无脂肪酸的牛血清白蛋白强烈抑制支链脂肪酸的线粒体和过氧化物酶体β-氧化，而硬脂酸氧化不受牛血清白蛋白影响或略有抑制。所呈现的结果清楚地表明，支链脂肪酸主要在大鼠肝脏的过氧化物酶体中降解。纯化的线粒体、过氧化物酶体和微粒体可将支链脂肪酸有效地转化为辅酶A硫酯。尽管降植烷酸和植烷酸分别迅速转化为降植烷酰辅酶A和植烷酰辅酶A，但它们不能被线粒体外膜转化为肉碱酯。结果表明，位于线粒体外膜的酰基辅酶A合成酶和肉碱酰基转移酶调节支链脂肪酸进入线粒体。线粒体肉碱酰基转移酶I似乎对直链脂肪酸具有高度特异性，并限制支链脂肪酸进入线粒体。因此，无法通过肉碱酰基转移酶系统转运穿过线粒体膜的支链脂肪酸被导向过氧化物酶体进行β-氧化。所报道的结果表明，植烷酸由于分子中存在β-甲基而可首先通过α-氧化降解，不能转运穿过线粒体膜。所呈现的数据强烈表明，植烷酸α-氧化发生在线粒体以外的细胞器中，可能发生在过氧化物酶体中。
