Aupetit B, Bastien C, Legrand J C
Biochimie. 1979;61(9):1085-9.
The authors have studied the in vitro conversion of 18 hydroxycorticostérone to aldosterone (18 oxidation) by duck adrenal subcellular fractions. Considering the new hypothesis about the mechanism of this step (hydroxylation mechanism) the authors have investigated a possible relationship between this reaction and cytochrome P450. With experimental conditions described, data show that metyrapone, a cytochrome P450 competitive inhibitor does not inhibit 18 oxidation. In contrast, 18 oxidation is inhibited by spirolactones (spironolactones, canrenone, potassium canrenoate). These compounds act at the cytochrome P450 level but have also an uncoupling effect which has been recently discovered. The effects of metyrapone and spirolactones on 18 oxidation as well as the different behaviour between biologicaly and organically synthetised 18 hydroxycorticosterone allow us to propose hypotheses for the mechanism of this step.
作者们研究了鸭肾上腺亚细胞组分将18 - 羟皮质酮转化为醛固酮(18氧化)的体外过程。考虑到关于这一步骤机制的新假说(羟化机制),作者们研究了该反应与细胞色素P450之间可能存在的关系。在所描述的实验条件下,数据表明,细胞色素P450竞争性抑制剂甲吡酮并不抑制18氧化。相反,螺内酯(安体舒通、坎利酮、坎利酸钾)可抑制18氧化。这些化合物作用于细胞色素P450水平,但最近发现它们也具有解偶联效应。甲吡酮和螺内酯对18氧化的影响以及生物合成和有机合成的18 - 羟皮质酮之间的不同表现,使我们能够对这一步骤的机制提出假说。