Glycerol-3-phosphate dehydrogenase (GPDH) is an enzyme that catalyzes the reversible redox conversion of dihydroxyacetone phosphate (a.k.a.
[3] Additionally, GPDH is one of the enzymes involved in maintaining the redox potential across the inner mitochondrial membrane.
Simultaneously, NADH is oxidized to NAD+ in the following reaction: As a result, NAD+ is regenerated for further metabolic activity.
The phosphate group of DHAP is half-encircled by the side-chain of Arg269, and interacts with Arg269 and Gly268 directly by hydrogen bonds (not shown).
Oxidation of cytoplasmic NADH by the cytosolic form of the enzyme creates glycerol-3-phosphate from dihydroxyacetone phosphate.
Once the glycerol-3-phosphate has moved through the outer mitochondrial membrane it can then be oxidised by a separate isoform of glycerol-3-phosphate dehydrogenase that uses quinone as an oxidant and FAD as a co-factor.
The mitochondrial isoform of G3P dehydrogenase is thought to be inhibited by metformin, a first line drug for type 2 diabetes.
Fig. 1. Schematic overview of fermentative and oxidative glucose metabolism of
Saccharomyces cerevisiae
. (A) upper part of
glycolysis
, which includes two sugar
phosphorylation
reactions. (B) fructose-1,6-bisphosphate aldolase, splitting the C6-molecule into two triose phosphates (C) triosephosphate isomerase, interconverting DHAP and GAP. (D) glycerol pathway reducing DHAP to
glycerol-3-phosphate
(G3P) by G3P dehydrogenase, followed by dephosphorylation to glycerol by G3Pase. (E) The lower part of glycolysis converts GAP to pyruvate while generating 1 NADH and 2 ATP via a series of 5 enzymes. (F) Alcoholic fermentation; decarboxylation of pyruvate by pyruvate decarboxylase, followed by reduction of acetaldehyde to ethanol. (G) mitochondrial pyruvate-dehydrogenase converts pyruvate to acetyl-CoA, which enters the tricarboxylic acid cycle. (H) external mitochondrial
NADH
dehydrogenases. (I) mitochondrial G3P dehydrogenase. Electrons of these three dehydrogenases enter the respiratory chain at the level of the quinol pool (Q). (J) internal mitochondrial NADH dehydrogenase. (K) ATP synthase. (L) generalized scheme of NADH shuttle. (M) formate oxidation by formate dehydrogenase.
[
4
]
Coupled reactions catalyzed by the cytosolic (GPDH-C) and mitochondrial (GPDH-M) forms of glycerol 3-phosphate dehydrogenase.
[
7
]
GPDH-C and GPDH-M use
NADH
and
quinol
(QH) as an
electron donors
respectively. GPDH-M in addition uses
FAD
as a co-factor.
