Wanders R J, Denis S, Wouters F, Wirtz K W, Seedorf U
Department of Clinical Chemistry, Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, The Netherlands.
Biochem Biophys Res Commun. 1997 Jul 30;236(3):565-9. doi: 10.1006/bbrc.1997.7007.
One of the most important functions of peroxisomes, at least in humans, is the beta-oxidation of a range of different fatty acids and fatty acid derivatives. Recent studies have shown that the enzymatic machinery required for the beta-oxidations of these substrates, may be much more complex as originally thought. We now report that the conventional peroxisomal thiolase which has so far been thought to catalyze the thiolytic cleavage of the 3-oxoacyl-CoA esters of all fatty acids oxidized in peroxisomes, shows poor reactivity towards the 3-oxoacyl-CoA esters of 2-methyl branched-chain fatty acids such as pristanic acid. Our data further show, that SCPx, a 58 kDa protein with both thiolase and sterol carrier protein activity but unknown function so far, readily reacts with 3-oxopristanoyl-CoA. Taken together, our data show that SCPx plays a central role in branched chain fatty acid beta-oxidation in peroxisomes. This finding has major implications not only for the functional organization of the peroxisomal beta-oxidation system but also for studies dealing with the resolution of the underlying defect in patients with some defect in peroxisomal beta-oxidation.
至少在人类中，过氧化物酶体最重要的功能之一是对一系列不同脂肪酸和脂肪酸衍生物进行β-氧化。最近的研究表明，这些底物β-氧化所需的酶机制可能比最初认为的要复杂得多。我们现在报告，迄今为止一直被认为催化过氧化物酶体中所有氧化脂肪酸的3-氧代酰基辅酶A酯硫解裂解的传统过氧化物酶体硫解酶，对2-甲基支链脂肪酸（如降植烷酸）的3-氧代酰基辅酶A酯反应性较差。我们的数据进一步表明，SCPx是一种58 kDa的蛋白质，具有硫解酶和固醇载体蛋白活性，但迄今为止功能未知，它很容易与3-氧代降植烷酰辅酶A反应。综合来看，我们的数据表明SCPx在过氧化物酶体中支链脂肪酸β-氧化中起核心作用。这一发现不仅对过氧化物酶体β-氧化系统的功能组织有重要意义，而且对研究过氧化物酶体β-氧化存在某些缺陷的患者潜在缺陷的解决也有重要意义。
