GAPDH and intermediary metabolism

Abstract

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. © 2013 Springer Science+Business Media Dordrecht.