The stimulation by calcium and its inhibition by ADP of cholesterol side-chain cleavage activity in adrenal mitochondria.
Cholesterol side-chain cleavage activity (cholesterol SCC) in a mitochondrial preparation is increased by calcium in a sigmoidal manner. A 5-10-fold increase is obtained and an effect may be seen at 20 microM CaCl2. ADP inhibits the stimulation by calcium with a shift of the sigmoid curve to the right and 10 microM ADP results in a 4-fold increase in the amount of CaCl2 required to obtain one-half the maximal stimulation value. The inhibition is specific for ADP and inhibition by ATP is due to the formation of ADP. The characteristics of the calcium-ADP modulation are such that a suitable ADP-inhibited level of cholesterol sidechain cleavage activity will be stimulated by a given increment of calcium to a greater extent than in the absence of the added ADP. Steroid 11 beta-hydroxylation is also stimulated in a sigmoidal manner by calcium and this stimulation is inhibited by ADP. The 11 beta-hydroxylation, however, is less sensitive to calcium and ADP so that changes in cholesterol SCC are obtained at concentration of calcium and ADP where minimal effects on 11 beta-hydroxylation are found. Calmodulin-like activity is present in the mitochondrial preparation. No evidence, however, for a role for calmodulin in the calcium-ADP effects could be obtained, but the possibility of its involvement cannot be excluded. The calcium-ADP modulations are of a magnitude and take place at sufficiently low concentrations to suggest a physiological role in the regulation of mitochondrial steroidogenesis.
D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000311:Adrenal Glands / Q000201:enzymology*; D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D002122:Calcium Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002417:Cattle; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000037:antagonists & inhibitors / Q000378:metabolism*; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D015636:Magnesium Chloride; D008861:Microsomes / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology; D009840:Oligomycins / Q000494:pharmacology; D010088:Oxidoreductases / Q000378:metabolism*; D010725:Phosphocreatine / Q000494:pharmacology; D013252:Steroid 11-beta-Hydroxylase / Q000378:metabolism
D009840:Oligomycins; D010725:Phosphocreatine; D015636:Magnesium Chloride; D000244:Adenosine Diphosphate; D000968:Antimycin A; D000255:Adenosine Triphosphate; D010088:Oxidoreductases; D013252:Steroid 11-beta-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme; D000251:Adenosine Triphosphatases; D008274:Magnesium; D002122:Calcium Chloride