Jakobs B S, Wanders R J
University of Amsterdam, Department of Paediatric Clinical Chemistry, The Netherlands.
Biochem Biophys Res Commun. 1995 Aug 24;213(3):1035-41. doi: 10.1006/bbrc.1995.2232.
We have investigated how [1-14C]propionyl-CoA, which is the first product of the peroxisomal beta-oxidation of [1-14C] pristanic acid, is transported to mitochondria for further oxidation in human skin fibroblasts from patients with a defect in the mitochondrial carnitine/acylcarnitine translocase and carnitine-palmitoyltransferase II (CPT II) (EC 2.3.1.21), respectively. Oxidation of pristanic acid was found to be partially deficient in both types of mutant cells. More important, 14CO2 production was completely deficient in the carnitine/acylcarnitine translocase deficient cells but not in the carnitine-palmitoyltransferase II deficient cells. These results strongly suggest that formation of 14CO2 in the Krebs cycle from [1-14C]propionyl-CoA as generated in peroxisomes requires the active participation of the mitochondrial carnitine/acylcarnitine translocase. The results described in this paper provide the first evidence suggesting that propionyl-CoA leaves the peroxisome as a carnitine ester and strongly suggest that the commonly accepted concept that peroxisomal beta-oxidation is not dependent on carnitine is incorrect.
我们研究了[1-¹⁴C]丙酸辅酶A（它是[1-¹⁴C]降植烷酸过氧化物酶体β-氧化的首个产物）如何被转运至线粒体，以便在分别患有线粒体肉碱/脂酰肉碱转位酶缺陷和肉碱-棕榈酰转移酶II（CPT II，EC 2.3.1.21）缺陷的人类皮肤成纤维细胞中进行进一步氧化。结果发现，在这两种类型的突变细胞中，降植烷酸的氧化均部分存在缺陷。更重要的是，在肉碱/脂酰肉碱转位酶缺陷的细胞中，¹⁴CO₂生成完全缺失，但在肉碱-棕榈酰转移酶II缺陷的细胞中并非如此。这些结果有力地表明，过氧化物酶体中生成的[1-¹⁴C]丙酸辅酶A在三羧酸循环中生成¹⁴CO₂需要线粒体肉碱/脂酰肉碱转位酶的积极参与。本文所述结果首次提供了证据，表明丙酰辅酶A以肉碱酯的形式离开过氧化物酶体，并有力地表明，普遍接受的过氧化物酶体β-氧化不依赖肉碱这一概念是错误的。
