The mechanism of Ca2+ stimulation of citrulline and N-acetylglutamate synthesis by mitochondria.
ATP-driven citrulline synthesis by mitochondria treated with oligomycin, uncoupler and Ca2+ ionophore is stimulated more than 2-fold by an increase in extramitochondrial free [Ca2+] in the range 1-5 microM. Stimulation increases with the length of preincubation of mitochondria with Ca2+. EGTA prevents stimulation if added at the start of the preincubation period, but is without effect if added at the end, suggesting that Ca2+ acts indirectly on citrulline synthesis via the accumulation of an intermediate. Neither carbamoyl-phosphate synthase (ammonia) nor ornithine carbamoyltransferase are stimulated by up to 50 microM free Ca2+ in mitochondrial extracts, but N-acetylglutamate synthase is stimulated about 30% by 10 microM free Ca2+. We propose that an increase in the activity of N-acetylglutamate synthase in response to an increase in free [Ca2+] in the mitochondrial matrix may contribute to hormonal stimulation of the urea cycle.
Johnston
J D
JD
Department of Biochemistry, University of Cambridge, U.K.
Brand
M D
MD
D000123:Acetyltransferases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000494:pharmacology; D051046:Amino-Acid N-Acetyltransferase; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002222:Carbamoyl-Phosphate Synthase (Ammonia) / Q000378:metabolism; D002956:Citrulline / Q000096:biosynthesis*; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D005971:Glutamates / Q000096:biosynthesis*; D008274:Magnesium / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology*; D009840:Oligomycins / Q000494:pharmacology; D009954:Ornithine Carbamoyltransferase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D005971:Glutamates; D009840:Oligomycins; D002956:Citrulline; D000001:Calcimycin; D004533:Egtazic Acid; D000255:Adenosine Triphosphate; D009954:Ornithine Carbamoyltransferase; D000123:Acetyltransferases; D051046:Amino-Acid N-Acetyltransferase; D002222:Carbamoyl-Phosphate Synthase (Ammonia); D008274:Magnesium; C016195:N-acetylglutamic acid; D002118:Calcium