Using guinea pig andrenal microsomes, we studied the inhibitory effects of 20α-hydroxyprogesterone on steroid hydroxylation reactions catalyzed by cytochromes P-450. When 17α-hydroxyprogesterone was used as a substr...Using guinea pig andrenal microsomes, we studied the inhibitory effects of 20α-hydroxyprogesterone on steroid hydroxylation reactions catalyzed by cytochromes P-450. When 17α-hydroxyprogesterone was used as a substrate, 20α-hydroxyprogesterone functioned as a competitive inhibitor on the C<sub>17</sub>—C<sub>20</sub> bond cleavage reaction of P-450<sub>17α lyase</sub>. The inhibition constant, K<sub>i</sub> was 1.37 μmol/L. 20α-hydroxyprogesterone also competitively inhibited the convertion of 17α-bydroxyprogesterone to 11-deoxycortisol by the action of P-450<sub>c21</sub>. The value of K<sub>i</sub> was 1.73μmol/L. When progesterone was used as a substrate, 20α-hydroxyprogesterone inhibited neither the 21-hydroxylation of P-450<sub>c21</sub>. the C<sub>17</sub>—C<sub>20</sub> bond cleavage, nor 17α-hydroxylation of P-450<sub>17α lyase</sub>. Based on the seresults, we can deduce that the production of androstenedione from progesterone by the action of P-450<sub>17α lyase</sub> proceeds through a successive monooxygenase reaction.展开更多
文摘Using guinea pig andrenal microsomes, we studied the inhibitory effects of 20α-hydroxyprogesterone on steroid hydroxylation reactions catalyzed by cytochromes P-450. When 17α-hydroxyprogesterone was used as a substrate, 20α-hydroxyprogesterone functioned as a competitive inhibitor on the C<sub>17</sub>—C<sub>20</sub> bond cleavage reaction of P-450<sub>17α lyase</sub>. The inhibition constant, K<sub>i</sub> was 1.37 μmol/L. 20α-hydroxyprogesterone also competitively inhibited the convertion of 17α-bydroxyprogesterone to 11-deoxycortisol by the action of P-450<sub>c21</sub>. The value of K<sub>i</sub> was 1.73μmol/L. When progesterone was used as a substrate, 20α-hydroxyprogesterone inhibited neither the 21-hydroxylation of P-450<sub>c21</sub>. the C<sub>17</sub>—C<sub>20</sub> bond cleavage, nor 17α-hydroxylation of P-450<sub>17α lyase</sub>. Based on the seresults, we can deduce that the production of androstenedione from progesterone by the action of P-450<sub>17α lyase</sub> proceeds through a successive monooxygenase reaction.
