H6PD

H6PD

Target · ER luminal enzyme

H6PD Hexose-6-phosphate dehydrogenase/glucose 1-dehydrogenase · GDH/6PGL endoplasmic bifunctional protein

H6PD (hexose-6-phosphate dehydrogenase/glucose 1-dehydrogenase, also H6PDH or GDH) is a bifunctional enzyme in the endoplasmic reticulum lumen. It catalyses the first two steps of the oxidative pentose phosphate pathway and supplies NADPH to the organelle. Browse Assay Genie's current range of H6PD research reagents below, or read on for the biology behind the target.

Endoplasmic reticulum lumenBifunctional oxidoreductaseAbsent from red cells
791 aa
Protein length
~89 kDa
Molecular weight
1p36.22
Gene locus
Oxidoreductase
Gene group
Target information

What is H6PD (hexose-6-phosphate dehydrogenase/glucose 1-dehydrogenase)?

H6PD is a bifunctional enzyme localised in the lumen of the endoplasmic reticulum. It catalyses the first two steps of the oxidative branch of the pentose phosphate pathway, an alternative to glycolysis and a major source of reducing power and metabolic intermediates for biosynthetic processes. Its hexose-6-phosphate dehydrogenase activity has broad substrate specificity compared with glucose-6-phosphate 1-dehydrogenase (G6PD) and performs the first step of the pathway. It also acts as a 6-phosphogluconolactonase, performing the second step. It may additionally act as a dehydrogenase on alternative substrates, including glucosamine 6-phosphate and glucose 6-sulfate.

The main role of H6PD is to provide reducing equivalents, such as NADPH, so that adequate levels of reductive cofactors are maintained in the oxidising environment of the endoplasmic reticulum. Because it produces the NADPH required by luminal reductases such as corticosteroid 11-beta-dehydrogenase isozyme 1 (HSD11B1), it indirectly regulates their activity. The C-terminal section of the protein belongs to the glucosamine/galactosamine-6-phosphate isomerase family, 6-phosphogluconolactonase subfamily. HGNC places the H6PD gene in the oxidoreductases group.

NCBI describes two forms of glucose-6-phosphate dehydrogenase. The G form is X-linked, while the H form, encoded by the H6PD gene, is autosomally linked. The H form is active on other hexose-6-phosphates, especially galactose-6-phosphate, whereas the G form is specific for glucose-6-phosphate. Both forms are present in most tissues, but the H form is not found in red cells. Earlier names for the gene include glucose dehydrogenase and hexose-6-phosphate dehydrogenase (glucose 1-dehydrogenase). The mouse ortholog is H6pd.

Pentose phosphate pathway

H6PD catalyses the first two steps of the oxidative pentose phosphate pathway inside the endoplasmic reticulum lumen, a source of reducing power and biosynthetic intermediates.

ER redox homeostasis

By generating NADPH, H6PD helps maintain reductive cofactor levels in the oxidising environment of the endoplasmic reticulum.

Glucocorticoid metabolism

H6PD supplies the NADPH needed by HSD11B1, so it indirectly regulates the activity of this luminal reductase.

Hexose-6-phosphate enzymology

Its broad substrate range, including galactose-6-phosphate, distinguishes H6PD from G6PD and makes it useful for comparing dehydrogenase specificity.

Background

H6PD frequently asked questions

What does H6PD do?

H6PD is an endoplasmic reticulum luminal enzyme that acts as a hexose-6-phosphate dehydrogenase and a 6-phosphogluconolactonase. It catalyses the first two steps of the oxidative pentose phosphate pathway and produces NADPH, which supports luminal reductases such as HSD11B1.

What other names does H6PD go by?

H6PD is also known as H6PDH and GDH. Its UniProt name is GDH/6PGL endoplasmic bifunctional protein, and earlier names include glucose dehyrogenase and hexose-6-phosphate dehydrogenase (glucose 1-dehydrogenase). The gene is on chromosome 1 and encodes the autosomal H form of glucose-6-phosphate dehydrogenase activity.

How does H6PD differ from G6PD?

G6PD is the X-linked G form and is specific for glucose-6-phosphate. H6PD is the autosomally linked H form and acts on other hexose-6-phosphates, especially galactose-6-phosphate. Both are present in most tissues, but H6PD is not found in red cells. A mouse ortholog, H6pd, exists; check the datasheet of any product for its validated reactivity.

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Related targets

Pentose phosphate pathway enzymes, other oxidoreductases and luminal reductase partners of H6PD with products at Assay Genie.

Gene and protein annotations from HGNC, NCBI Gene and UniProt O95479; product specifications from Assay Genie datasheets.

H6PD Product listing