GAPDH

GAPDH Full Name

glyceraldehyde-3-phosphate dehydrogenase

GAPDH Introduction

GAPDH is a housekeeping gene that is expressed in all cells. It is also one of the most conserved proteins that have been identified. GAPDH is a glycolytic enzyme that catalyzes the sixth step in glycolysis, the conversion of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate. GAPDH is considered to be a typical housekeeping gene, because GAPDH levels do not vary greatly in most tissues, and it is used as an internal control in many experiments. GAPDH is not only highly expressed, it is also a moonlighting protein. The roles of GAPDH are much more diverse than simply a housekeeping metabolic catalyst, it has many other critical functions in the cell.

Figure 1. Enzymatic reactions mediated by GPD1 and GPD2.(Source: Oh S, et al.; 2024)

Beyond its role in metabolism, GAPDH is also involved in nuclear events, redox signaling, membrane trafficking and cytoskeleton dynamics. GAPDH is also known to shuttle to the nucleus in response to stress, where it is implicated in transcriptional regulation, DNA repair and apoptotic signaling. GAPDH interacts with RNA and a number of signaling proteins. It is a point of convergence of stress-response pathways. Post-translational modifications, including S-nitrosylation, phosphorylation and acetylation regulate its subcellular localization and its multiple activities, allowing GAPDH to sense oxidative/nitrosative stress.

Abnormal GAPDH activity and expression has been noted in various disease states. GAPDH has been found to aberrantly accumulate in the nucleus in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and Huntington's disease, and has additional roles in neuronal dysfunction through apoptotic mechanisms. GAPDH has also been associated with cancer. Overexpression of the enzyme can lead to the altered glycolysis called the Warburg effect, which in turn can lead to an increase in cancer cell growth. GAPDH has been connected to a large spectrum of other diseases as well, such as inflammation, diabetes, ischemic injury, and viral infection. In many of these disease states, alterations to either metabolic flux or levels of oxidative stress can alter pathogenesis of the disease. Overall, GAPDH has been linked to both metabolic and non-metabolic activities that are connected to stress and pathological processes.

Alternate Names for GAPDH

glyceraldehyde-3-phosphate dehydrogenase; GAPD; Peptidyl-cysteine S-nitrosylase GAPDH; aging-associated gene 9 protein; G3PD; glyceraldehyde 3-phosphate dehydrogenase; G3P_HUMAN;

• 1. Oh S, et al.; Glycerol 3-phosphate dehydrogenases (1 and 2) in cancer and other diseases.Exp Mol Med. 2024, 56(5):1066-1079.