7-Dehydrocholesterol reductase

Function

The protein encoded by this gene is an enzyme catalyzing the reversible production of cholesterol from 7-dehydrocholesterol using nicotinamide adenine dinucleotide phosphate (NADPH) as its cofactor.

The DHCR7 gene encodes delta-7-sterol reductase (EC 1.3.1.21), the ultimate enzyme of mammalian sterol biosynthesis that converts 7-dehydrocholesterol (7-DHC) to cholesterol. This enzyme removes the C(7-8) double bond introduced by the sterol delta8-delta7 isomerases. In addition, its role in drug-induced malformations is known: inhibitors of the last step of cholesterol biosynthesis such as AY9944 and BM15766 severely impair brain development.

It displays a modest level of enzyme promiscuity, being able to catalyze analogous reactions with (substrate in forward direction) brassicasterol, 20S(OH)7DHC, 27(OH)DHC and 7-dehydrodesmosterol.

Pathology

A deficiency is associated with Smith–Lemli–Opitz syndrome.

All house cats and dogs have higher-than-usual activity of this enzyme, causing an inability to synthesize vitamin D due to the lack of 7-dehydrocholesterol.

Interactive pathway map

References

References

1. "Entrez Gene: DHCR7 7-dehydrocholesterol reductase".
2. (Feb 1998). "Molecular cloning and expression of the human delta7-sterol reductase". Proceedings of the National Academy of Sciences of the United States of America.
3. (Jul 1998). "Mutations in the human sterol delta7-reductase gene at 11q12-13 cause Smith-Lemli-Opitz syndrome". American Journal of Human Genetics.
4. {{KEGG enzyme. 1.3.1.21
5. (1 December 2023). "Effects of Long-Term High-Ergosterol Intake on the Cholesterol and Vitamin D Biosynthetic Pathways of Rats Fed a High-Fat and High-Sucrose Diet". Biological and Pharmaceutical Bulletin.
6. (September 2021). "Selective ability of rat 7-Dehydrocholesterol reductase (DHCR7) to act on some 7-Dehydrocholesterol metabolites but not on lumisterol metabolites". The Journal of Steroid Biochemistry and Molecular Biology.
7. (Nov 2005). "Recent insights into the Smith-Lemli-Opitz syndrome". Clinical Genetics.
8. (January 2020). "Vitamin D metabolism in dogs and cats and its relation to diseases not associated with bone metabolism". Journal of Animal Physiology and Animal Nutrition.