Simpson E R, Williams-Smith D L
Biochim Biophys Acta. 1975 Oct 9;404(2):309-20. doi: 10.1016/0304-4165(75)90338-4.
The effect of calcium on pregnenolone formation from endogenous precursors has been studied in mitochondria from rat decapsulated and capsular adrenal glands. In the presence of succinate, addition of calcium chloride in the concentration range 20-150 muM caused an inhibition of pregnenolone formation in both decapsulated and capsular adrenal mitochondria. 11beta-hydroxylation of added deoxycosticosterone in decapsulated adrenal mitochondria was also inhibited. Under these conditions, calcium inhibited the reduction of adrenodoxin, a component of the cytochrome P-450 reductase system, presumably because uptake of calcium by the mitochondria competes with energy-linked transhydrogenase for high-energy intermediates. For this reason, incubations were carried out in the presence of succinate plus isocitrate plus NADP+. Under these conditions, calcium chloride in the concentration range 120-875 muM caused a 2-4-fold stimulation of pregnenolone formation, but had no effect on corticosterone formation from added deoxycorticosterone. The effect of calcium on the optical spectra of cytochrome P-450 has also been examined in mitochondria from decapsulated and capsular rat adrenals. In the presence of succinate, calcium induced a spectral change resembling a type I difference spectrum of cytochrome P-450. Thus it appears that uptake of calcium by adrenal mitochondria can stimulate pregnenolone formation by increasing the interaction of mitochondrial cytochrome P-450 with endogenous substrate.
在大鼠去包膜和带包膜肾上腺的线粒体中，研究了钙对内源性前体生成孕烯醇酮的影响。在琥珀酸存在的情况下，添加浓度范围为20 - 150 μM的氯化钙会抑制去包膜和带包膜肾上腺线粒体中孕烯醇酮的生成。去包膜肾上腺线粒体中添加的脱氧皮质酮的11β-羟化作用也受到抑制。在这些条件下，钙抑制了肾上腺铁氧化还原蛋白（细胞色素P - 450还原酶系统的一个组分）的还原，推测是因为线粒体对钙的摄取与能量偶联转氢酶竞争高能中间体。因此，在琥珀酸加异柠檬酸加NADP⁺存在的情况下进行孵育。在这些条件下，浓度范围为120 - 875 μM的氯化钙使孕烯醇酮的生成增加了2 - 4倍，但对添加的脱氧皮质酮生成皮质酮没有影响。还在大鼠去包膜和带包膜肾上腺的线粒体中研究了钙对细胞色素P - 450光谱的影响。在琥珀酸存在的情况下，钙诱导了一种类似于细胞色素P - 450 I型差光谱的光谱变化。因此，肾上腺线粒体对钙的摄取似乎可以通过增加线粒体细胞色素P - 450与内源性底物的相互作用来刺激孕烯醇酮的生成。
