Metabolic interplay of GAPDH and Sir2.

<p>GAPDH catalyzes the oxidation of NADH: it generates NAD⁺ in close proximity to Sir2. Under conditions with high glycolytic flux, higher amounts of glyceraldehyde-3-phosphate (gly-3-P) are produced, driving the backward reaction. In this case, GAPDH reduces more NAD⁺ to NADH and inhibits the deacetylation reaction by depleting NAD⁺; NAD⁺ is a limiting factor for the Sirtuins to catalyze the formation of O-acetyl-ADP-ribose (AADPR) via the transfer of acetyl groups.