The role of malic enzyme in the malate dependent biosynthesis of progesterone in the mitochondrial fraction of human term placenta.
Mitochondria isolated from human term placenta were able to form citrate from malate as the only added substrate. While mitochondria were incubated in the presence of Mn2+ the citrate formation was stimulated significantly both by NAD+ and NADP+ and was inhibited by hydroxymalonate, arsenite, butylmalonate and rotenone. It is concluded that NAD(P)-linked malic enzyme is involved in the conversion of malate to citrate in these mitochondria. It has also been shown that the conversion of cholesterol to progesterone by human term placental mitochondria incubated in the presence of malate was stimulated by NAD+ and NADP+ and inhibited by arsenite and fluorocitrate. This suggests that the stimulation by malate of progesterone biosynthesis depends not only on the generation of NADPH by NAD(P)-linked malic enzyme, but also on NADPH formed during further metabolism of pyruvate to isocitrate which is in turn efficiently oxidized by NADP+-linked isocitrate dehydrogenase.
D002951:Citrates / Q000378:metabolism; D019343:Citric Acid; D005260:Female; D006801:Humans; D008291:Malate Dehydrogenase / Q000378:metabolism*; D008293:Malates / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011374:Progesterone / Q000096:biosynthesis*
D002951:Citrates; D008293:Malates; D009243:NAD; D019343:Citric Acid; D011374:Progesterone; D009249:NADP; C030298:malic acid; D008291:Malate Dehydrogenase