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
Robert C TuckeyAndrzej T Slominski

Abstract

7-Dehydrocholesterol reductase (DHCR7) catalyses the final step of cholesterol biosynthesis in the Kandutsch-Russel pathway, the reduction of 7-dehydrocholesterol (7DHC) to cholesterol. 7DHC can be acted on by a range of other enzymes including CYP27A1 and CYP11A1, as well as by UVB radiation, producing a number of derivatives including hydroxy-metabolites, some of which retain the C7-C8 double bond and are biologically active. These metabolites include lumisterol (L3) which is a stereoisomer of 7DHC produced in the skin by UVB radiation of 7DHC, as well as vitamin D3. The aim of this study was to test whether these metabolites could act as substrates or inhibitors of DHCR7 in rat liver microsomes. To initially screen the ability of these metabolites to interact with the active site of DHCR7, their ability to inhibit the conversion of ergosterol to brassicasterol was measured. Sterols that significantly inhibited this reaction included 7DHC (as expected), 20S(OH)7DHC, 27(OH)DHC, 8DHC, 20S(OH)L3 and 22(OH)L3 but not 7-dehydropregnenolone (7DHP), 25(OH)7DHC, L3 or vitamin D3 and its hydroxyderivatives. Sterols that inhibited ergosterol reduction were directly tested as substrates for DHCR7. 20S(OH)7DHC, 27(OH)DHC and 7-dehydrodes...Continue Reading

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Citations

Aug 28, 2021·International Journal of Molecular Sciences·Georgeta BochevaAndrzej T Slominski

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