TAILIEUCHUNG - Báo cáo khoa học: A novel pathway for sequential transformation of 7-dehydrocholesterol and expression of the P450scc system in mammalian skin

Following up on our previous findings that the skin pos-sesses steroidogenic activity from progesterone, we now show widespread cutaneous expression of the full cyto-chrome P450 side-chain cleavage (P450scc) system required for the intracellular catalytic production of pregnenolone, . the genes andproteins for P450scc enzyme, adrenodoxin, adrenodoxin reductase and MLN64. Functionality of the system was confirmed in mitochondria from skin cells. | Eur. J. Biochem. 271 4178-4188 2004 FEBS 2004 doi A novel pathway for sequential transformation of 7-dehydrocholesterol and expression of the P450scc system in mammalian skin Andrzej Slominski1 Jordan Zjawiony3 Jacobo Wortsman4 Igor Semak5 Jeremy Stewart3 Alexander Pisarchik1 Trevor Sweatman2 Josep Marcos6 Chuck Dunbar3 Robert C Tuckey7 . Departments of1 Pathology and Laboratory Medicine and 2Pharmacology University of Tennessee Health Science Center Memphis TN USA 3Department of Pharmacognosy University of Mississippi University MS USA 4Department of Medicine Southern Illinois University Springfield IL USA 5Department of Biochemistry Belarus State University Minsk Belarus 6Children s Hospital Oakland Research Institute Oakland CA USA 7Department of Biochemistry and Molecular Biology School of Biomedical and Chemical Science University of Western Australia Crawley Australia Following up on our previous findings that the skin possesses steroidogenic activity from progesterone we now show widespread cutaneous expression of the full cytochrome P450 side-chain cleavage P450scc system required for the intracellular catalytic production of pregnenolone . the genes and proteins for P450scc enzyme adrenodoxin adrenodoxin reductase and MLN64. Functionality of the system was confirmed in mitochondria from skin cells. Moreover purified mammalian P450scc enzyme and most importantly mitochondria isolated from placenta and adrenals produced robust transformation of 7-dehydro-cholesterol 7-DHC precursor to cholesterol and vitamin D3 to 7-dehydropregnenolone 7-DHP . Product identity was confirmed by comparison with the chemically synthesized standard and chromatographic MS and NMR analyses. Reaction kinetics for the conversion of 7-DHC into 7-DHP were similar to those for cholesterol conversion into pregnenolone. Thus 7-DHC can form 7-DHP through P450scc side-chain cleavage which may serve as a substrate for further conversions into hydroxy .

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