Glutamate-malate metabolism in liver mitochondria. A model constructed on the basis of mitochondrial levels of enzymes, specificity, dissociation constants, and stoichiometry of hetero-enzyme complexes.
The level of aspartate aminotransferase in liver mitochondria was found to be approximately 140 microM, or 2-3 orders of magnitude higher than its dissociation constant in complexes with the inner mitochondrial membrane and the high molecular weight enzymes (M(r) = 1.6 x 10(5) to 2.7 x 10(6)) carbamyl-phosphate synthase I, glutamate dehydrogenase, and the alpha-ketoglutarate dehydrogenase complex. The total concentration of aminotransferase-binding sites on these structures in liver mitochondria was more than sufficient to accommodate all of the aminotransferase. Therefore, in liver mitochondria, the aminotransferase could be associated with the inner mitochondrial membrane and/or these high molecular weight enzymes. The aminotransferase in these hetero-enzyme complexes could be supplied with oxalacetate because binding of aminotransferase to the high molecular weight enzymes can enhance binding of malate dehydrogenase, and binding of both malate dehydrogenase and the aminotransferase facilitated binding of fumarase. The level of malate dehydrogenase was found to be so high (140 microM) in liver mitochondria, compared with that of citrate synthase (25 microM) and the pyruvate dehydrogenase complex (0.3 microM), that there would also be a sufficient supply of oxalacetate to citrate synthase-pyruvate dehydrogenase.
Department of Pharmacology, University of Wisconsin Medical School, Madison 53706.
L A
LA
Fahien
J K
JK
Teller
D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002222:Carbamoyl-Phosphate Synthase (Ammonia) / Q000378:metabolism; D002950:Citrate (si)-Synthase / Q000378:metabolism; D005649:Fumarate Hydratase / Q000378:metabolism; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D007425:Intracellular Membranes / Q000201:enzymology; D007655:Ketoglutarate Dehydrogenase Complex / Q000378:metabolism; D008291:Malate Dehydrogenase / Q000378:metabolism; D008293:Malates / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology / Q000378:metabolism*; D008956:Models, Chemical; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D051381:Rats; D011915:Rats, Inbred BUF
D005971:Glutamates; D008293:Malates; D011768:Pyruvate Dehydrogenase Complex; D018698:Glutamic Acid; C030298:malic acid; D008291:Malate Dehydrogenase; D007655:Ketoglutarate Dehydrogenase Complex; D005969:Glutamate Dehydrogenase; D002950:Citrate (si)-Synthase; D001219:Aspartate Aminotransferases; D005649:Fumarate Hydratase; D002222:Carbamoyl-Phosphate Synthase (Ammonia)