Abstract
1. The pathways and the fate of glutamate carbon and nitrogen were investigated in isolated guinea-pig kidney-cortex tubules. 2. At low glutamate concentration (1 mM), the glutamate carbon skeleton was either completely oxidized or converted into glutamine. At high glutamate concentration (5 mM), glucose, lactate and alanine were additional products of glutamate metabolism. 3. At neither concentration of glutamate was there accumulation of ammonia. 4. Nitrogen-balance calculations and the release of 14CO2 from L-[1-14C]glutamate (which gives an estimation of the flux of glutamate carbon skeleton through alpha-oxoglutarate dehydrogenase) clearly indicated that, despite the absence of ammonia accumulation, glutamate metabolism was initiated by the action of glutamate dehydrogenase and not by transamination reactions as suggested by Klahr, Schoolwerth & Bourgoignie [(1972) Am. J. Physiol. 222, 813-820] and Preuss [(1972) Am. J. Physiol. 222, 1395-1397]. Additional evidence for this was obtained by the use of (i) amino-oxyacetate, an inhibitor of transaminases, which did not decrease glutamate removal, or (ii) L-methionine DL-sulphoximine, an inhibitor of glutamine synthetase, which caused an accumulation of ammonia from glutamate. 5. Addition of NH4Cl plus glutamate caused an increase in both glutamate removal and glutamine synthesis, demonstrating that the supply of ammonia via glutamate dehydrogenase is the rate-limiting step in glutamine formation from glutamate. NH4Cl also inhibited the flux of glutamate through glutamate dehydrogenase and the formation of glucose, alanine and lactate. 6. The activities of enzymes possibly involved in the glutamate conversion into pyruvate were measured in guinea-pig renal cortex. 7. Renal arteriovenous-difference measurements revealed that in vivo the guinea-pig kidney adds glutamine and alanine to the circulating blood.
Full text
PDF







Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- BRAUNSTEIN A. E. BINDING AND REACTIONS OF THE VITAMIN B6 COENZYME IN THE CATALYTIC CENTER OF ASPARTATE TRANSAMINASE. Vitam Horm. 1964;22:451–484. doi: 10.1016/s0083-6729(08)60348-9. [DOI] [PubMed] [Google Scholar]
- Baverel G., Bonnard M., D'Armagnac de Castanet E., Pellet M. Lactate and pyruvate metabolism in isolated renal tubules of normal dogs. Kidney Int. 1978 Dec;14(6):567–575. doi: 10.1038/ki.1978.165. [DOI] [PubMed] [Google Scholar]
- Baverel G., Lund P. A role for bicarbonate in the regulation of mammalian glutamine metabolism. Biochem J. 1979 Dec 15;184(3):599–606. doi: 10.1042/bj1840599. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dean B., Bartley W. Oxaloacetate decarboxylases of rat liver. Biochem J. 1973 Dec;135(4):667–672. doi: 10.1042/bj1350667. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Feliú J. E., Hue L., Hers H. G. Hormonal control of pyruvate kinase activity and of gluconeogenesis in isolated hepatocytes. Proc Natl Acad Sci U S A. 1976 Aug;73(8):2762–2766. doi: 10.1073/pnas.73.8.2762. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Guder W., Wiesner W., Stukowski B., Wieland O. Metabolism of isolated kidney tubules. Oxygen consumption, gluconeogenesis and the effect of cyclic nucleotides in tubules from starved rats. Hoppe Seylers Z Physiol Chem. 1971 Oct;352(10):1319–1328. doi: 10.1515/bchm2.1971.352.2.1319. [DOI] [PubMed] [Google Scholar]
- HOLTEN D. D., NORDLIE R. C. COMPARATIVE STUDIES OF CATALYTIC PROPERTIES OF GUINEA PIG LIVER INTRA- AND EXTRAMITOCHONDRIAL PHOSPHOENOLPYRUVATE CARBOXYKINASES. Biochemistry. 1965 Apr;4:723–731. doi: 10.1021/bi00880a018. [DOI] [PubMed] [Google Scholar]
- Klahr S., Schoolwerth A. C., Bourgoignie J. J. Relation of gluconeogenesis to ammonia production in the kidney. Am J Physiol. 1972 Apr;222(4):813–820. doi: 10.1152/ajplegacy.1972.222.4.813. [DOI] [PubMed] [Google Scholar]
- Klahr S., Schoolwerth A. C. Renal gluconeogenesis: effects of quinolinic acid. Biochim Biophys Acta. 1972 Aug 18;279(1):157–162. doi: 10.1016/0304-4165(72)90250-4. [DOI] [PubMed] [Google Scholar]
- Krebs H. A. Metabolism of amino-acids: The synthesis of glutamine from glutamic acid and ammonia, and the enzymic hydrolysis of glutamine in animal tissues. Biochem J. 1935 Aug;29(8):1951–1969. doi: 10.1042/bj0291951. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mattenheimer H., Pollak V. E., Muehrcke R. C. Quantitative enzyme patterns in the nephron of the healthy human kidney. Nephron. 1970;7(2):144–154. doi: 10.1159/000179816. [DOI] [PubMed] [Google Scholar]
- Meister A. The specificity of glutamine synthetase and its relationship to substrate conformation at the active site. Adv Enzymol Relat Areas Mol Biol. 1968;31:183–218. doi: 10.1002/9780470122761.ch5. [DOI] [PubMed] [Google Scholar]
- OWEN E. E., ROBINSON R. R. Amino acid extraction and ammonia metabolism by the human kidney during the prolonged administration of ammonium chloride. J Clin Invest. 1963 Feb;42:263–276. doi: 10.1172/JCI104713. [DOI] [PMC free article] [PubMed] [Google Scholar]
- POLLAK V. E., MATTENHEIMER H., DEBRUIN H., WEINMAN K. J. EXPERIMENTAL METABOLIC ACIDOSIS: THE ENZYMATIC BASIS OF AMMONIA PRODUCTION BY THE DOG KIDNEY. J Clin Invest. 1965 Feb;44:169–181. doi: 10.1172/JCI105132. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Preuss H. G. Glutamine and glutamate metabolism in guinea pig kidney slices. Am J Physiol. 1972 Jun;222(6):1395–1397. doi: 10.1152/ajplegacy.1972.222.6.1395. [DOI] [PubMed] [Google Scholar]
- RICHTERICH R. W., GOLDSTEIN L. Distribution of glutamine metabolizing enzymes and production of urinary ammonia in the mammalian kidney. Am J Physiol. 1958 Nov;195(2):316–320. doi: 10.1152/ajplegacy.1958.195.2.316. [DOI] [PubMed] [Google Scholar]
- Squires E. J., Hall D. E., Brosnan J. T. Arteriovenous differences for amino acids and lactate across kidneys of normal and acidotic rats. Biochem J. 1976 Oct 15;160(1):125–128. doi: 10.1042/bj1600125. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Szepesi B., Avery E. H., Freedland R. A. Role of kidney in gluconeogenesis and amino acid catabolism. Am J Physiol. 1970 Dec;219(6):1627–1631. doi: 10.1152/ajplegacy.1970.219.6.1627. [DOI] [PubMed] [Google Scholar]
