Question

What would happen specifically to metabolic pathways and cofactors, etc, involved if the levels/abilities of the glycolytic enzyme, GAPDH, were depleted? like for example I know that Krebs cycle could no longer continue since glucose can no longer be converted to pyruvate and then to acetyl-CoA. What else would be affected? what would increase and decrease?

Answer 1

GAPDH has a pivotal role in the intermediary metabolism of human tissues.GAPDH catalyzes the conversion of glyceraldehyde-3-phosphate to glycerate-1,3-bisphosphate and represents a regulatory hurdle in anaerobic glycolysis. The triose substrate of GAPDH is actually a product of several important metabolic pathways such as glycolysis, fructose catabolism, pentose phosphate pathway and glycerol metabolism. The GAPDH reaction is important for hepatic gluconeogenesis. Thus, depletion of GADPH levels affects the above-stated pathways. Levels of dihydroxyacetone phosphate (DHAP)are partially controlled by glyceraldehyde-3-phosphate dehydrogenase (GAPDH), the former being an important source of methylglyoxal. Methylglyoxal (MG) may be an important cause of diabetic complications. Furthermore, perturbations in the levels of GADPH might also interfere with the determination of cancer cell fate.