A PRELIMINARY REPORT ON INTERMEDIATES IN CONVERSION IN VITRO OF CHOLESTEROL TO PREGNENOLONE IN ADRENAL PREPARATIONS

The reaction sequences cholesterol → 20α-hydroxycholesterol → 20α, 22R-di-hydroxycholesterol → pregnenolone, and cholesterol → 22R-hydroxycholesterol → 20α, 22Rrdihydroxycholesterol → pregnenolone have been studied quantitatively under conditions of first-order kinetics with adrenocortical preparations. The sequence of 22R-hydroxycholesterol was much more important than that of 20α-hydroxycholesterol, but only a small fraction of the pregnenolone formation from cholesterol via the monohydroxy derivatives could be accounted for. A much more substantial fraction could be accounted for by assuming an enzymatic, concerted attack of oxygen on cholesterol to form 20α, 22R-dihydroxycholesterol which then is oxidatively cleaved to pregnenolone. This study establishes several pathways leading from cholesterol to pregnenolone. © 1968.