Hydroxylation of 19-norandrostenedione by adrenal cortex mitochondrial P-450(11)beta.
The activity of purified bovine adrenocortical P-450(11)beta on the C18-steroid, 4-estrene-3,17-dione (19-norandrostenedione), is described. The major steroid products were separated by HPLC and identified by GC-MS, and 1H- and 13C-NMR as 11 beta-, 18- and 6 beta-hydroxylated derivatives of 19-norandrostenedione. The turnover numbers of the 11 beta-, 18- and 6 beta-hydroxylase reactions were 45, 7.5 and 1.9 (mol/min/mol of P-450(11)beta), respectively, with a common Km of 44 microM. All of these activities required the presence of the electron donating system consisting of NADPH, adrenal ferredoxin (adrenodoxin) and its reductase. These findings provide additional insights into the versatile catalytic roles of P-450(11)beta in the adrenal cortex, in which it may act on C18-19-nor-steroids in addition to its known activities on C21- and C19-steroids.
Suhara
K
K
Department of Chemistry, Faculty of Science, Kanazawa University, Japan.
Yamamoto
M
M
Katagiri
M
M
D000302:Adrenal Cortex / Q000201:enzymology*; D000325:Adrenodoxin / Q000378:metabolism; D000735:Androstenedione / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D005287:Ferredoxin-NADP Reductase / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006863:Hydrogen-Ion Concentration; D006900:Hydroxylation; D009682:Magnetic Resonance Spectroscopy; D008928:Mitochondria / Q000201:enzymology; D015394:Molecular Structure; D009249:NADP / Q000378:metabolism; D013252:Steroid 11-beta-Hydroxylase / Q000378:metabolism*; D013250:Steroid Hydroxylases / Q000378:metabolism*; D013379:Substrate Specificity
D000325:Adrenodoxin; D000735:Androstenedione; D009249:NADP; D013250:Steroid Hydroxylases; D013252:Steroid 11-beta-Hydroxylase; D005287:Ferredoxin-NADP Reductase; C002828:19-norandrostenedione