Effect of phospholipids and organic solvents on the formation of 5,16-androstadien-3 beta-ol from pregnenolone in adrenal and testicular microsomes.
The formation of 5,16-androstadien-3 beta-ol from pregnenolone (andien-beta synthase activity) is catalyzed by cytochrome P450c17, which also catalyzes C-17-hydroxy/lyase activity in the biosynthesis of androgens. Andien-beta synthase is very active in porcine Leydig cells, but it is almost undetectable in porcine and bovine adrenal, although the adrenal gland also expresses P450c17. We have treated microsomal preparations with lipids and organic solvents to examine if the andien-beta synthase and C-17-hydroxy/lyase activities of P450c17 were affected by these agents. The addition of some phospholipids to the microsomal preparations inhibited both P450c17 activities. Phospholipids with different fatty acids had no effect on the ratio of andien-beta synthase to C-17-hydroxy/lyase activity. The addition of solvents to the microsomal preparations generally inhibited both P450c17 activities. However, the addition of acetyl acetone up to 5% (v/v) preferentially increased the andien-beta synthase activity while decreasing, the C-17-hydroxy/lyase activity. The effect was dose-dependent, specific to acetyl acetone and was seen in both testis and adrenal microsomes. The exact nature of the stimulation of andien-beta synthase activity is unknown, but the andien-beta synthase activity obtained after treatment with acetyl acetone was directly correlated to total P450c17 activity in the untreated microsomes. The inhibition of C-17-hydroxy/lyase activity by acetyl acetone was particularly apparent with the C-17,20-lyase reaction rather than the 17 alpha-hydroxylase reaction. The addition of acetyl acetone can potentially be used to assess the total potential of P450c17 to catalyze andien-beta synthase activity in vitro.[1]References
- Effect of phospholipids and organic solvents on the formation of 5,16-androstadien-3 beta-ol from pregnenolone in adrenal and testicular microsomes. Meadus, W.J., Squires, E.J. Steroids (1995) [Pubmed]
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