Significance of the alanine aminotransferase reaction in the formation of alpha-ketoglutarate in rat liver mitochondria.
The total production of alpha-ketoglutarate from glutamate and isocitrate was estimated in isolated rat liver mitochondria. Mitochondrial alanine aminotransferase converts glutamate to alpha-ketoglutarate [A.K. Groen et al. (1982) Eur. J. Biochem. 122, 87-93], thus participating in the net formation of the tricarboxylic acid cycle intermediates from glutamate. The present investigation indicates a significant contribution of the alanine aminotransferase reaction to glutamate oxidation by isolated rat liver mitochondria in the presence of bicarbonate. It amounted to 41-74 and 7-31% of the total utilization of glutamate in States 4 and 3, respectively, in various conditions in vitro, at pyruvate concentrations in the range of 0.1-10 mM. The participation of glutamate in the total production of alpha-ketoglutarate at physiological concentrations of glutamate, citrate, and isocitrate varied in the range of 72-82%. It was calculated that alpha-ketoglutarate formation by the reaction of alanine aminotransferase amounted to 30 and 5% of the total mitochondrial alpha-ketoglutarate production in States 4 and 3, respectively, at physiological concentrations of its precursors and in the presence of 0.5 mM malate and 0.1 mM pyruvate. It constituted 77-97% of the net production of the tricarboxylic acid cycle intermediates from glutamate in rat liver mitochondria. The importance of alpha-ketoglutarate production via the alanine aminotransferase reaction under various physiological conditions is discussed.
D000409:Alanine / Q000096:biosynthesis; D000410:Alanine Transaminase / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000096:biosynthesis; D002951:Citrates / Q000378:metabolism; D019343:Citric Acid; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D007656:Ketoglutaric Acids / Q000096:biosynthesis*; D008293:Malates / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology / Q000378:metabolism*; D010071:Oxaloacetates / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D011919:Rats, Inbred Strains
D002951:Citrates; D005971:Glutamates; D007656:Ketoglutaric Acids; D008293:Malates; D010071:Oxaloacetates; D011773:Pyruvates; D019343:Citric Acid; D001224:Aspartic Acid; D018698:Glutamic Acid; C030298:malic acid; D019289:Pyruvic Acid; D000410:Alanine Transaminase; D000409:Alanine