8em2

Structural highlights

Disease

G6PE_HUMAN Hyperandrogenism due to cortisone reductase deficiency. The disease is caused by variants affecting the gene represented in this entry.

Function

G6PE_HUMAN 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).[UniProtKB:Q8CFX1]^{[1] [2] [3]}

References

1. ↑ Draper N, Walker EA, Bujalska IJ, Tomlinson JW, Chalder SM, Arlt W, Lavery GG, Bedendo O, Ray DW, Laing I, Malunowicz E, White PC, Hewison M, Mason PJ, Connell JM, Shackleton CH, Stewart PM. Mutations in the genes encoding 11beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase interact to cause cortisone reductase deficiency. Nat Genet. 2003 Aug;34(4):434-9. PMID:12858176 doi:10.1038/ng1214
2. ↑ Lavery GG, Walker EA, Tiganescu A, Ride JP, Shackleton CH, Tomlinson JW, Connell JM, Ray DW, Biason-Lauber A, Malunowicz EM, Arlt W, Stewart PM. Steroid biomarkers and genetic studies reveal inactivating mutations in hexose-6-phosphate dehydrogenase in patients with cortisone reductase deficiency. J Clin Endocrinol Metab. 2008 Oct;93(10):3827-32. PMID:18628520 doi:10.1210/jc.2008-0743
3. ↑ Lavery GG, Idkowiak J, Sherlock M, Bujalska I, Ride JP, Saqib K, Hartmann MF, Hughes B, Wudy SA, De Schepper J, Arlt W, Krone N, Shackleton CH, Walker EA, Stewart PM. Novel H6PDH mutations in two girls with premature adrenarche: 'apparent' and 'true' CRD can be differentiated by urinary steroid profiling. Eur J Endocrinol. 2013 Feb 1;168(2):K19-26. PMID:23132696 doi:10.1530/EJE-12-0628