TAILIEUCHUNG - Báo cáo khoa học: Testosterone 1b-hydroxylation by human cytochrome P450 3A4

Human cytochrome P450 3A4 forms a series of minor testosterone hydroxylation products in addition to 6b-hy-droxytestosterone, the major product. One of these, formed at the next highest rate after the 6b-and 2b-hydroxy prod-ucts, was identified as 1b-hydroxytestosterone. This product was characterized from a mixture of testosterone oxidation products using an HPLC-solid phase extraction-cryoprobe NMR/time-of-flight mass spectrometry system, with an estimated total of 6lgof this spectrometry established the formula as C19H29O3(MH + ) | Eur. J. Biochem. 271 3962-3969 2004 FEBS 2004 doi Testosterone ip-hydroxylation by human cytochrome P450 3A4 Joel A Krauser1. Markus Voehler2 Li-Hona Tsena3. Alexandre B. Schefer3. Markus Godejohann3 . . and F. Peter Guengerich1 1 Department of Biochemistry and Center in Molecular Toxicology Vanderbilt University School of Medicine and department of Chemistry and Center in Molecular Toxicology Vanderbilt University Nashville TN USA 3Bruker Bio-Spin GmbH Rheinstetten Germany Human cytochrome P450 3A4 forms a series of minor testosterone hydroxylation products in addition to 6b-hy-droxytestosterone the major product. One of these formed at the next highest rate after the 6 b- and 2b-hydroxy products was identified as 1 b-hydroxytestosterone. This product was characterized from a mixture of testosterone oxidation products using an HPLC-solid phase extraction-cryoprobe NMR time-of-flight mass spectrometry system with an estimated total of w 6 Ig of this product. Mass spectrometry established the formula as C19H29O3 MH . . The 1-position of the added hydroxyl group was established by correlated spectroscopy and heteronuclear spin quantum correlation experiments and the b-stereochemistry of the added hydroxyl group was assigned with a nuclear Overhauser correlated spectroscopy experiment 1a-H . Of several human P450s examined only P450 3A4 formed this product. The product was also formed in human liver microsomes. Keywords cytochrome P450 NMR spectroscopy HPLC-NMR combinations testosterone. Cytochrome P450 P450 also termed heme-thiolate P450 1 enzymes have long been of interest because of their roles in steroid metabolism 2 3 . These oxidations are most critical in steroidogenic tissues and a set of w 12 P450s are most important 4 5 . The hepatic P450s have also been studied extensively in the context of their abilities to hydroxylate steroids even though few of the oxidations involve the generation of products with distinctive .

• Báo cáo khoa học
• Report medicine
• traditional medicine
• scientific reports
• Structural biochemistry
• bacteria
• chemical reaction
• medical knowledge
• medical research
• analysis of cytoplasmic
• oxidation
• Crystal structure
• hemoglobin
• medicine
• cell proliferation
• breast cancer
• gastric cancer
• hormone medicine
• tumor cells
• biochemical studies
• environmental medicine