Identification of intermediates in the conversion of cholesterol to pregnenolone with a reconstituted cytochrome p-450scc system: accumulation of the intermediate modulated by the adrenodoxin level

Journal of Biochemistry
S SuganoN Morishima

Abstract

Dihydroxycholesterol and pregnenolone were clearly detected on HPLC when 22R-hydroxycholesterol was incubated with a reconstituted P450scc system containing equimolar amounts of P450scc and adrenodoxin. The dihydroxycholesterol, which has been accepted to be an intermediate in the conversion of 22R-hydroxycholesterol to pregnenolone, accumulated when adrenodoxin was at a subsaturating level with respect to P450scc. The formation of the intermediate increased with increasing pH in the range of 7.2 to 8.1, and the ratio of the intermediate to the product, pregnenolone, increased with increasing pH. When the binding of P450scc to adrenodoxin was weakened by elevation of the ionic strength, the formation of the intermediate relative to the product increased. The apparent Km for dihydroxycholesterol at a subsaturating level of adrenodoxin was about 7 microM, in contrast to 4 microM at a saturating level of adrenodoxin, implying that the affinity of dihydroxycholesterol is lower at a subsaturating level of adrenodoxin than at a saturating one. These results suggest that a subsaturating level of adrenodoxin weakened the binding of dihydroxycholesterol to P450scc and thus the intermediate, dihydroxycholesterol, was released. An interme...Continue Reading

Citations

May 15, 2002·Journal of Biotechnology·Joachim JoseFrank Hannemann
Dec 11, 2007·Steroids·Norman B Javitt
Oct 17, 2015·The Journal of Steroid Biochemistry and Molecular Biology·Francis K Yoshimoto, Richard J Auchus
Jan 5, 2000·Physiological Reviews·G J Schroepfer
Dec 4, 2020·The Journal of Steroid Biochemistry and Molecular Biology·E O YablokovN V Strushkevich
Mar 17, 2021·Molecular and Cellular Endocrinology·Rita Bernhardt, Jens Neunzig
Apr 24, 2002·Biochemical and Biophysical Research Communications·Norman B Javitt

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