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H6PD

Function

Bifunctional enzyme localized in the lumen of the endoplasmic reticulum that catalyzes the first two steps of the oxidative branch of the pentose phosphate pathway/shunt, an alternative to glycolysis and a major source of reducing power and metabolic intermediates for biosynthetic processes (By similarity). Has a hexose-6-phosphate dehydrogenase activity, with broad substrate specificity compared to glucose-6-phosphate 1-dehydrogenase/G6PD, and catalyzes the first step of the pentose phosphate pathway (PubMed:12858176, PubMed:18628520, PubMed:23132696). In addition, acts as a 6-phosphogluconolactonase and catalyzes the second step of the pentose phosphate pathway (By similarity). May have a dehydrogenase activity for alternative substrates including glucosamine 6-phosphate and glucose 6-sulfate (By similarity). The main function of this enzyme is to provide reducing equivalents such as NADPH to maintain the adequate levels of reductive cofactors in the oxidizing environment of the endoplasmic reticulum (PubMed:12858176, PubMed:18628520, PubMed:23132696). By producing NADPH that is needed by reductases of the lumen of the endoplasmic reticulum like corticosteroid 11-beta-dehydrogenase isozyme 1/HSD11B1, indirectly regulates their activity (PubMed:18628520).

Involvement in disease

Cortisone reductase deficiency 1

CORTRD1

An autosomal recessive error of cortisone metabolism characterized by a failure to regenerate cortisol from cortisone, resulting in increased cortisol clearance, activation of the hypothalamic-pituitary axis and ACTH-mediated adrenal androgen excess. Clinical features include hyperandrogenism resulting in hirsutism, oligo-amenorrhea, and infertility in females and premature pseudopuberty in males.

None

The disease is caused by variants affecting the gene represented in this entry.

Pathway

Carbohydrate degradation; pentose phosphate pathway; D-ribulose 5-phosphate from D-glucose 6-phosphate (oxidative stage): step 1/3.

Carbohydrate degradation; pentose phosphate pathway; D-ribulose 5-phosphate from D-glucose 6-phosphate (oxidative stage): step 2/3.

Carbohydrate degradation; pentose phosphate pathway; D-ribulose 5-phosphate from D-glucose 6-phosphate (oxidative stage).

Sequence Similarities

In the N-terminal section; belongs to the glucose-6-phosphate dehydrogenase family.

In the C-terminal section; belongs to the glucosamine/galactosamine-6-phosphate isomerase family. 6-phosphogluconolactonase subfamily.

Tissue Specificity

Present in most tissues examined, strongest in liver.

Cellular localization

Alternative names

GDH, H6PD, GDH/6PGL endoplasmic bifunctional protein

swissprot:O95479 entrezGene:9563 entrezGene:25796 omim:604951 swissprot:O95336 omim:138090