Wallace J C, Jitrapakdee S, Chapman-Smith A
Department of Biochemistry, University of Adelaide, Australia.
Int J Biochem Cell Biol. 1998 Jan;30(1):1-5. doi: 10.1016/s1357-2725(97)00147-7.
Pyruvate carboxylase [EC 6.4.1.1] is a member of the family of biotin-dependent carboxylases and is found widely among eukaryotic tissues and in many prokaryotic species. It catalyses the ATP-dependent carboxylation of pyruvate to form oxaloacetate which may be utilised in the synthesis of glucose, fat, some amino acids or their derivatives and several neurotransmitters. Diabetes and hyperthyroidism increase the level of expression of pyruvate carboxylase in the long term, while its activity in the short term is controlled by the intramitochondrial concentrations of acetyl-CoA and pyruvate. Many details of this enzyme's regulation are yet to be described in molecular terms. However, progress towards this goal and towards understanding the relationship of pyruvate carboxylase structure to its catalytic reaction mechanism, has been enormously enhanced recently by the cloning and sequencing of genes and cDNAs encoding the approximately 130 kDa subunit of this homotetramer. Defects in the expression or biotinylation of pyruvate carboxylase in humans almost invariably results in early death or at best a severely debilitating psychomotor retardation, clearly reflecting the vital role it plays in intermediary metabolism in many tissues including the brain.
丙酮酸羧化酶[EC 6.4.1.1]是生物素依赖性羧化酶家族的成员，广泛存在于真核生物组织和许多原核生物物种中。它催化丙酮酸的ATP依赖性羧化反应，生成草酰乙酸，草酰乙酸可用于葡萄糖、脂肪、某些氨基酸或其衍生物以及几种神经递质的合成。糖尿病和甲状腺功能亢进长期会增加丙酮酸羧化酶的表达水平，而其短期活性则受线粒体内乙酰辅酶A和丙酮酸浓度的控制。该酶调节的许多细节仍有待从分子层面进行描述。然而，最近通过对编码这种同四聚体约130 kDa亚基的基因和cDNA进行克隆和测序，在实现这一目标以及理解丙酮酸羧化酶结构与其催化反应机制之间关系方面取得了巨大进展。人类丙酮酸羧化酶表达或生物素化的缺陷几乎总是导致早期死亡，或者至多导致严重的精神运动发育迟缓，这清楚地反映了它在包括大脑在内的许多组织的中间代谢中所起的重要作用。
