Question

I have reviewed the mechanism involving NAD+, G3P, and cysteine and I know the steps by memory, but what is the role of GAPDH specifically? Is the fact that the reaction is catalyzed by GAPDH simply a must-know? Does the reaction take place inside the enzyme active site?

Answer 1

GAPDH is an essential enzyme in glycolysis, catalyzing the oxidative phosphorylation of G3P, producing NADH and 1,3-bisphosphoglycerate within its active site, and its activity is allosterically regulated by NAD+ through negative cooperativity.

Step-by-step explanation:

The enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays a pivotal role in glycolysis, specifically in the sixth step of the pathway. GAPDH catalyzes the reaction in which glyceraldehyde-3-phosphate (G3P) is oxidized, resulting in the reduction of nicotinamide adenine dinucleotide (NAD+) to NADH, while simultaneously phosphorylating the oxidized G3P to form 1,3-bisphosphoglycerate. This important reaction occurs within the active site of the GAPDH enzyme, where specific amino acid residues facilitate the transfer of electrons and the addition of a phosphate group. The role of GAPDH is critical because it not only contributes to ATP production later in glycolysis but also links to other metabolic pathways through the production of NADH.

GAPDH is regulated allosterically, with NAD+ acting as a regulator. This regulation is an example of negative cooperativity, where a high concentration of NAD+ leads to a lower affinity of the enzyme for further NAD+, thus modulating the rate of the glycolytic reaction based on the cellular energy status and NAD+ availability.