Department of Biochemistry, Kansas City University of Medicine and Biosciences, Kansas City, MO, USA.
Adv Exp Med Biol. 2013;985:37-59. doi: 10.1007/978-94-007-4716-6_2.
GAPDH plays a major enzymatic role in the intermediary metabolism of human tissues. In fact, the cells of all organisms require the catalytic capability of GAPDH in order to maintain adequate glycolytic flux. Even the primitive archaea rely on GAPDH in a pivotal step in the Entner-Doudoroff pathway, which is a series of reactions that resembles glycolysis. GAPDH catalyzes the sixth reaction of glycolysis in eukaryotic cells and represents a regulatory hurdle in anaerobic glycolysis. The triose substrate of GAPDH is actually a product of several important metabolic pathways: stage one of glycolysis, fructose catabolism, pentose phosphate pathway and glycerol metabolism. The GAPDH reaction is reversible, hence, necessary for hepatic gluconeogenesis. The chapter discusses GAPDH as being a metabolic 'switching station', diverting carbon flow appropriately. There is discussion regarding the experimental analysis of GAPDH's enzymatic function, particularly in the use of inhibitors. The GAPDH gene is portrayed in the context of the enzyme's role in metabolism. The observed intolerance to genetic mutation suggests that the genetic changes (i.e. those seen across species) may provide a treasure of information regarding the limits of genetic variability that can be tolerated and still allow for the protein to conduct essential glycolytic - as well as non-glycolytic - functions.
GAPDH 在人体组织的中间代谢中发挥主要的酶催化作用。事实上，为了维持足够的糖酵解通量，所有生物体的细胞都需要 GAPDH 的催化能力。即使是原始的古细菌也依赖 GAPDH 来完成 Entner-Doudoroff 途径中的关键步骤，该途径是一系列类似于糖酵解的反应。GAPDH 在真核细胞的糖酵解第六步反应中起催化作用，是无氧糖酵解的一个调节障碍。GAPDH 的三碳底物实际上是几个重要代谢途径的产物：糖酵解的第一阶段、果糖分解代谢、戊糖磷酸途径和甘油代谢。GAPDH 反应是可逆的，因此对肝糖异生是必要的。本章讨论了 GAPDH 作为代谢“转换站”，适当地改变碳流。还讨论了 GAPDH 酶促功能的实验分析，特别是抑制剂的使用。GAPDH 基因在酶的代谢作用的背景下被描绘。对遗传突变的观察不宽容表明，遗传变化（即跨物种观察到的变化）可能提供了有关遗传可变性的极限的宝贵信息，这些遗传变化可以被容忍，并且仍然允许该蛋白进行必要的糖酵解——以及非糖酵解——功能。
