6-Phosphogluconate dehydrogenase

6-Phosphogluconate Dehydrogenase

Structure of 6-phosphogluconate dehydrogenase

Another view of the enzyme structure

6-Phosphogluconate dehydrogenase is an enzyme that plays a crucial role in the pentose phosphate pathway, a metabolic pathway parallel to glycolysis. This enzyme catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate and carbon dioxide, with the concomitant reduction of NADP+ to NADPH.

Function

6-Phosphogluconate dehydrogenase is involved in the oxidative phase of the pentose phosphate pathway. This pathway is essential for the production of NADPH, which is required for biosynthetic reactions and for maintaining the redox balance in cells. The enzyme also contributes to the generation of ribose 5-phosphate, a precursor for the synthesis of nucleotides and nucleic acids.

Structure

The enzyme is typically a dimer, with each subunit containing a binding site for NADP+ and 6-phosphogluconate. The active site of the enzyme is located at the interface between the two subunits, allowing for efficient catalysis. The structure of 6-phosphogluconate dehydrogenase has been elucidated through X-ray crystallography, revealing details about its catalytic mechanism and substrate binding.

Mechanism

The catalytic mechanism of 6-phosphogluconate dehydrogenase involves the oxidation of the C3 hydroxyl group of 6-phosphogluconate to a ketone, followed by decarboxylation to form ribulose 5-phosphate. The reaction proceeds with the transfer of a hydride ion from the substrate to NADP+, forming NADPH. This reaction is an example of an oxidative decarboxylation, a common type of reaction in metabolic pathways.

Clinical Significance

Deficiencies in 6-phosphogluconate dehydrogenase can lead to disruptions in the pentose phosphate pathway, affecting the production of NADPH and ribose 5-phosphate. This can have downstream effects on cellular metabolism, particularly in cells that rely heavily on NADPH for antioxidant defense and lipid synthesis.

Related Enzymes

6-Phosphogluconate dehydrogenase is part of a family of dehydrogenases that includes glucose-6-phosphate dehydrogenase and isocitrate dehydrogenase, which also participate in oxidative decarboxylation reactions and are involved in various metabolic pathways.

Related Pages

• Pentose phosphate pathway
• NADPH
• Ribulose 5-phosphate
• Oxidative decarboxylation

Gallery

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  Structure of 6-phosphogluconate dehydrogenase
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  Another view of the enzyme structure