Patel M S, Naik S, Wexler I D, Kerr D S
Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York at Buffalo 14214, USA.
J Nutr. 1995 Jun;125(6 Suppl):1753S-1757S. doi: 10.1093/jn/125.suppl_6.1753S.
The mammalian pyruvate dehydrogenase complex (PDC) is subject to both short-term (product inhibition and covalent modification) and long-term (increases in total activity and protein mass) regulation mediated by dietary and hormonal treatments. Recent advances in the isolation and characterization of the complementary DNAs as well as genes encoding several components of mammalian PDC have facilitated studies concerning long-term regulation of PDC. Analyses of the promoter-regulatory regions of the two human PDC genes show characteristics of both facultative and housekeeping gene promoters, indicating complex transcriptional regulation. Deficiency of PDC activity causes a wide range of neurological disabilities. A spectrum of genetic defects in PDC components has been reported; however, the most frequent defects are associated with the pyruvate dehydrogenase component. Heterogeneity in pyruvate dehydrogenase deficiency has been shown to occur at both protein and messenger RNA levels, and several mutations in pyruvate dehydrogenase have been identified. Dietary treatments such as ketogenic diets and vitamin supplements as well as dichloroacetate treatment have been utilized to treat PDC deficiency, but their efficacy requires further evaluation.
哺乳动物丙酮酸脱氢酶复合体（PDC）受到饮食和激素处理介导的短期（产物抑制和共价修饰）和长期（总活性和蛋白质质量增加）调节。哺乳动物PDC几个组分的互补DNA以及编码基因的分离和表征方面的最新进展促进了有关PDC长期调节的研究。对两个人类PDC基因启动子调控区的分析显示了兼性基因和管家基因启动子的特征，表明存在复杂的转录调控。PDC活性缺乏会导致多种神经功能障碍。已经报道了PDC组分中的一系列遗传缺陷；然而，最常见的缺陷与丙酮酸脱氢酶组分有关。丙酮酸脱氢酶缺乏的异质性已在蛋白质和信使RNA水平上得到证实，并且已鉴定出丙酮酸脱氢酶中的几种突变。生酮饮食和维生素补充剂等饮食疗法以及二氯乙酸治疗已被用于治疗PDC缺乏症，但其疗效需要进一步评估。
