Ca(2+) modulates respiratory and steroidogenic activities of human term placental mitochondria.
We investigated the effects of calcium on the oxidative metabolism and steroidogenic activity of human term placental mitochondria. Submicromolar Ca(2+) concentrations stimulated state 3 oxygen consumption with 2-oxoglutarate and isocitrate and activated the 2-oxoglutarate and the NAD-isocitrate dehydrogenases by diminishing their Michaelis-Menten constants. Ca(2+) inhibited NADP-isocitrate dehydrogenase (NADP-ICDH) and the synthesis of progesterone. The NADP-ICDH maximal velocity was threefold higher than that of NAD-ICDH and had a threefold lower K(m) for isocitrate than NAD-ICDH. Isocitrate but not malate or 2-oxoglutarate supported progesterone synthesis. Calcium inhibition of progesterone synthesis was observed with isocitrate but not with malate or 2-oxoglutarate. Tight regulation of NADP-isocitrate dehydrogenase by calcium ions suggests that this enzyme plays an important role in placental mitochondrial metabolism.
García-Pérez
Cecilia
C
Departamento de Bioqui;mica, Facultad de Medicina, Universidad Nacional Autónoma de México, Apdo. Postal 70-159, DF 04510, México, Mexico.
Pardo
Juan Pablo
JP
Martínez
Federico
F
D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000737:chemistry; D007700:Kinetics; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D009249:NADP / Q000737:chemistry; D010101:Oxygen Consumption; D010920:Placenta / Q000378:metabolism*; D011374:Progesterone / Q000096:biosynthesis / Q000494:pharmacology; D013256:Steroids / Q000378:metabolism; D013997:Time Factors
D013256:Steroids; D011374:Progesterone; D009249:NADP; D007521:Isocitrate Dehydrogenase; D002118:Calcium