GAPDH
GAPDH (glyceraldehyde-3-phosphate dehydrogenase) is the glycolytic enzyme that oxidizes and phosphorylates glyceraldehyde-3-phosphate. It is treated as a housekeeping protein in molecular biology, and it also participates in signaling.
Function
In glycolysis, GAPDH catalyzes the reaction that captures energy as NADH and 1,3-bisphosphoglycerate: it oxidizes its substrate, reduces NAD+ to NADH, and adds an inorganic phosphate. The reaction is the glycolytic step that links sugar oxidation to ATP production, and GAPDH’s activity sets the pace of the pathway under many conditions. The protein is abundant (often 1–5% of cellular protein), stable, and uniformly expressed — which is why it served for decades as the standard loading control and reference gene in molecular biology.
In signaling, aging, and cancer
GAPDH’s abundance makes it available for other uses. The enzyme translocates to the nucleus under oxidative stress and during S-phase, where it participates in DNA repair, transcriptional coactivation, and — in neurons — a cell-death program in which S-nitrosylated GAPDH carries a nuclear partner to degrade the genome. It binds telomeric DNA, single-stranded DNA breaks, and ATM-pathway components. In cancer, GAPDH is upregulated as part of the glycolytic shift (the Warburg effect) and acts as an HIF-1α coactivator; because researchers assumed its expression was constant, its changing expression in tumors went unnoticed for years.
Notes
- Human gene symbol: GAPDH; UniProt P04406; 335 amino acids; tetramer; four catalytic cysteine-containing active sites.