Mesh : Animals Cell Differentiation / physiology Cell Division / physiology Disease Growth / physiology Homeostasis / drug effects Hormones / pharmacology Humans Malate Dehydrogenase / physiology NAD / metabolism NADP / metabolism Pyruvic Acid / metabolism

来  源:   DOI:10.4149/endo_2009_01_39   PDF(Sci-hub)

Abstract:
Malate dehydrogenases (MDHs) are specific class of ubiquitous and multimeric oxidative decarboxylases with well conserved amino acid sequences in structurally important regions and with similar overall structural topology. They mostly use malate or oxaloacetate as substrates to generate pyruvate and utilize preferentially NADP or NAD as cofactor. Among species and even within an organism they differ in their subcellular localization and specificity for the cofactor. Comparison across microbial, plant and animal kingdoms show that MDHs were able to adopt tissue-, species- or environmental-specific functions while still keeping main structural features. Although basic principles of MDH regulation are similar to other enzymes and include oligomerization, cofactor binding, divalent cation availability, some of MDH enzymes are regulated also at different levels involving control of hysteresis, protein-protein interaction and gene expression. In this review we concentrate on those aspects of MDH function and regulation in animals that are specifically associated with cell differentiation and proliferation, ontogenic development, hormonal control, and partly with diseases. Accenting these aspects of MDHs provides emerging and new views on their regulatory function in complex eukaryotic metazoan organisms that goes beyond their classical role in basic metabolism.
摘要:
苹果酸脱氢酶(MDHs)是特定类别的普遍存在的和多聚体的氧化脱羧酶,在结构重要的区域中具有非常保守的氨基酸序列并且具有相似的总体结构拓扑。它们主要使用苹果酸或草酰乙酸作为底物以产生丙酮酸并优先利用NADP或NAD作为辅因子。在物种之间,甚至在生物体内,它们的亚细胞定位和对辅因子的特异性都不同。跨微生物的比较,动植物王国表明MDHs能够采用组织-,物种或环境特定的功能,同时仍保持主要的结构特征。尽管MDH调节的基本原理与其他酶相似,包括寡聚化,辅因子结合,二价阳离子可用性,一些MDH酶也在不同的水平上受到调节,包括滞后的控制,蛋白质相互作用和基因表达。在这篇综述中,我们专注于与细胞分化和增殖特别相关的动物中MDH功能和调节的那些方面。个体发育,荷尔蒙控制,部分与疾病有关。加入MDH的这些方面为它们在复杂的真核后生生物中的调节功能提供了新兴的新观点,这些功能超出了它们在基础代谢中的经典作用。
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