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It is an oxidative carboxylase that catalyses the oxidative decarboxylation of 6-phosphogluconate into ribulose 5-phosphate in the presence of NADP. This reaction is a component of the hexose mono-phosphate shunt and pentose phosphate pathways (PPP).
6-Phosphogluconic acid (with conjugate base 6-phosphogluconate) is a phosphorylated sugar acid which appears in the pentose phosphate pathway and the Entner–Doudoroff pathway.
The pentose phosphate pathway (also called the phosphogluconate pathway and the hexose monophosphate shunt or HMP shunt) is a metabolic pathway parallel to glycolysis. [1] It generates NADPH and pentoses (five- carbon sugars ) as well as ribose 5-phosphate , a precursor for the synthesis of nucleotides . [ 1 ]
6-phospho-D-glucono-1,5-lactone + H 2 O = 6-phospho-D-gluconate. The tertiary structure of 6PGL employs an α/β hydrolase fold, with active site residues clustered on the loops of the α-helices. Based on the crystal structure of the enzyme, the mechanism is proposed to be dependent on proton transfer by a histidine residue in the active site.
The general structure, as well as several critical residues, on 6-phosphogluconate dehydrogenase appear to be well conserved over various species. The enzyme is a dimer, with each subunit containing three domains. The N-terminal coenzyme binding domain contains a Rossmann fold with additional α/β units.
This will cause the G6P to be dehydrogenated to 6-phosphogluconate by glucose 6-phosphate dehydrogenase. [1] This irreversible reaction is the initial step of the pentose phosphate pathway, which generates the useful cofactor NADPH as well as ribulose-5-phosphate, a carbon source for the synthesis of other molecules. [1]
G6PD converts G6P into 6-phosphoglucono-δ-lactone and is the rate-limiting enzyme of the pentose phosphate pathway. Thus, regulation of G6PD has downstream consequences for the activity of the rest of the pentose phosphate pathway. Glucose-6-phosphate dehydrogenase is stimulated by its substrate G6P.
6-Phosphogluconate dehydrogenase (6PGD) is an enzyme in the pentose phosphate pathway (see image). 6PGD catalyzes the reaction of 6-phosphogluconate to an unstable form of 3-keto-6-phosphogluconate, and yields a co-enzyme nicotinamide adenine dinucleotide phosphate (NADPH) as a byproduct. NADPH supplies reducing power to cells.