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. 1971 Jul;123(3):391–397. doi: 10.1042/bj1230391

Effects of metabolic acidosis and starvation on the content of intermediary metabolites in rat kidney

D A Hems 1,*, J T Brosnan 1,†
PMCID: PMC1176970  PMID: 5126092

Abstract

1. Metabolite contents were determined in freeze-clamped kidney from acidotic and starved rats in order to elucidate the rate-controlling steps which are responsible for the acceleration of gluconeogenesis in these situations. 2. In the kidney of rats which were made mildly acidotic by replacing drinking water with 1.5% ammonium chloride for 7 to 10 days (when the plasma bicarbonate concentration was 20mm) the content of phosphoenolpyruvate was increased from the control value of 35 to 63nmol/g and that of 3-phosphoglycerate from 85 to 154nmol/g. 3. Similar but smaller changes in these metabolites occurred in the kidney of starved rats but there were no such changes in the kidney of rats 12h after an infusion of 0.25m-hydrochloric acid, although plasma bicarbonate concentration fell to about 10mm on this treatment. 4. The renal concentration of glucose 6-phosphate was not raised in rats that received ammonium chloride, but was increased in starved and acutely acidotic rats. 5. The concentrations of α-oxoglutarate, malate and citrate were less than half the normal value in the kidney of both groups of acidotic rats. These changes can be accounted for on the basis of equilibrium relationships among reversible reactions, particularly as a result of the rise in intracellular ammonia content. A less marked decrease in α-oxoglutarate and malate was found in the kidney of starved rats. 6. The renal cortical cytoplasmic oxaloacetate concentration was calculated to be decreased in acidotic and starved rats. 7. These results are discussed in the light of the known enhancement by acidosis and starvation of renal gluconeogenesis. In particular they support the suggestion that the phosphoenolpyruvate carboxykinase reaction is a site of control of gluconeogenesis in kidney in these conditions.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Addae S. K., Lotspeich W. D. Glutamine balance in metabolic acidosis as studied with the artificial kidney. Am J Physiol. 1968 Aug;215(2):278–281. doi: 10.1152/ajplegacy.1968.215.2.278. [DOI] [PubMed] [Google Scholar]
  2. Addae S. K., Lotspeich W. D. Relation between glutamine utilization and production in metabolic acidosis. Am J Physiol. 1968 Aug;215(2):269–277. doi: 10.1152/ajplegacy.1968.215.2.269. [DOI] [PubMed] [Google Scholar]
  3. Alleyne G. A. Concentrations of metabolic intermediates in kidneys of rats with metabolic acidosis. Nature. 1968 Mar 2;217(5131):847–848. doi: 10.1038/217847a0. [DOI] [PubMed] [Google Scholar]
  4. Alleyne G. A. Renal metabolic response to acid-base changes. II. The early effects of metabolic acidosis on renal metabolism in the rat. J Clin Invest. 1970 May;49(5):943–951. doi: 10.1172/JCI106314. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Alleyne G. A., Scullard G. H. Renal metabolic response to acid base changes. I. Enzymatic control of ammoniagenesis in the rat. J Clin Invest. 1969 Feb;48(2):364–370. doi: 10.1172/JCI105993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Churchill P. C., Malvin R. L. Relation of renal gluconeogenesis to ammonia production in the dog. Am J Physiol. 1970 Jan;218(1):241–245. doi: 10.1152/ajplegacy.1970.218.1.241. [DOI] [PubMed] [Google Scholar]
  7. DAVIES B. M. A., YUDKIN J. Studies in biochemical adaptation; the origin or urinary ammonia as indicated by the effect of chronic acidosis and alkalosis on some renal enzymes in the rat. Biochem J. 1952 Nov;52(3):407–412. doi: 10.1042/bj0520407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. DENIS G., PREUSS H., PITTS R. THE PNH3 OF RENAL TUBULAR CELLS. J Clin Invest. 1964 Apr;43:571–582. doi: 10.1172/JCI104942. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dyson J. E., Anderson W. B., Nordlie R. C. Inhibitory effect of physiological bicarbonate ion levels on the activities of glucose 6-phosphate phosphohydrolase. J Biol Chem. 1969 Feb 25;244(4):560–566. [PubMed] [Google Scholar]
  10. Goldstein L. Pathways of glutamine deamination and their control in the rat kidney. Am J Physiol. 1967 Oct;213(4):983–989. doi: 10.1152/ajplegacy.1967.213.4.983. [DOI] [PubMed] [Google Scholar]
  11. Goldstein L. Relation of glutamate to ammonia production in the rat kidney. Am J Physiol. 1966 Mar;210(3):661–666. doi: 10.1152/ajplegacy.1966.210.3.661. [DOI] [PubMed] [Google Scholar]
  12. Goodman A. D., Fuisz R. E., Cahill G. F., Jr Renal gluconeogenesis in acidosis, alkalosis, and potassium deficiency: its possible role in regulation of renal ammonia production. J Clin Invest. 1966 Apr;45(4):612–619. doi: 10.1172/JCI105375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Goorno W. E., Rector F. C., Jr, Seldin D. W. Relation of renal gluconeogenesis to ammonia production in the dog and rat. Am J Physiol. 1967 Oct;213(4):969–974. doi: 10.1152/ajplegacy.1967.213.4.969. [DOI] [PubMed] [Google Scholar]
  14. Haldane J. B. Experiments on the regulation of the blood's alkalinity: II. J Physiol. 1921 Aug 3;55(3-4):265–275. doi: 10.1113/jphysiol.1921.sp001969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hems D. A., Brosnan J. T. Effects of ischaemia on content of metabolites in rat liver and kidney in vivo. Biochem J. 1970 Nov;120(1):105–111. doi: 10.1042/bj1200105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Henning H. V., Stumpf B., Ohly B., Seubert W. On the mechanism of gluconeogenesis and its regulation. 3. The glucogenic capacity and the activities of pyruvate carboxylase and PEP-carboxylase of rat kidney and rat liver after cortisol treatment and starvation. Biochem Z. 1966 Apr 27;344(3):274–288. [PubMed] [Google Scholar]
  17. KREBS H. A., BENNETT D. A., DE GASQUET P., GASQUET P., GASCOYNE T., YOSHIDA T. Renal gluconeogenesis. The effect of diet on the gluconeogenic capacity of rat-kidney-cortex slices. Biochem J. 1963 Jan;86:22–27. doi: 10.1042/bj0860022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kamm D. E., Cahill G. F., Jr Effect of acid-base status on renal and hepatic gluconeogenesis in diabetes and fasting. Am J Physiol. 1969 May;216(5):1207–1212. doi: 10.1152/ajplegacy.1969.216.5.1207. [DOI] [PubMed] [Google Scholar]
  19. Kamm D. E., Fuisz R. E., Goodman A. D., Cahill G. F., Jr Acid-base alterations and renal gluconeogenesis: effect of pH, bicarbonate concentration, and PCO2. J Clin Invest. 1967 Jul;46(7):1172–1177. doi: 10.1172/JCI105610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. LEONARD E., ORLOFF J. Regulation of ammonia excretion in the rat. Am J Physiol. 1955 Jul;182(1):131–138. doi: 10.1152/ajplegacy.1955.182.1.131. [DOI] [PubMed] [Google Scholar]
  21. Lotspeich W. D. Metabolic aspects of acid-base change. Science. 1967 Mar 3;155(3766):1066–1075. doi: 10.1126/science.155.3766.1066. [DOI] [PubMed] [Google Scholar]
  22. Newsholme E. A., Gevers W. Control of glycolysis and gluconeogenesis in liver and kidney cortex. Vitam Horm. 1967;25:1–87. doi: 10.1016/s0083-6729(08)60033-3. [DOI] [PubMed] [Google Scholar]
  23. PITTS R. F. RENAL PRODUCTION AND EXCRETION OF AMMONIA. Am J Med. 1964 May;36:720–742. doi: 10.1016/0002-9343(64)90182-2. [DOI] [PubMed] [Google Scholar]
  24. Pagliara A. S., Goodman A. D. Relation of renal cortical gluconeogenesis, glutamate content, and production of ammonia. J Clin Invest. 1970 Nov;49(11):1967–1974. doi: 10.1172/JCI106416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Preuss H. G. Renal glutamate metabolism in acute metabolic acidosis. Nephron. 1969;6(3):235–246. doi: 10.1159/000179731. [DOI] [PubMed] [Google Scholar]
  26. RECTOR F. C., Jr, SELDIN D. W., COPENHAVER J. H. The mechanism of ammonia excretion during ammonium chloride acidosis. J Clin Invest. 1955 Jan;34(1):20–26. doi: 10.1172/JCI103058. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Veech R. L., Eggleston L. V., Krebs H. A. The redox state of free nicotinamide-adenine dinucleotide phosphate in the cytoplasm of rat liver. Biochem J. 1969 Dec;115(4):609–619. doi: 10.1042/bj1150609a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Veech R. L., Raijman L., Krebs H. A. Equilibrium relations between the cytoplasmic adenine nucleotide system and nicotinamide-adenine nucleotide system in rat liver. Biochem J. 1970 Apr;117(3):499–503. doi: 10.1042/bj1170499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Williamson D. H., Lund P., Krebs H. A. The redox state of free nicotinamide-adenine dinucleotide in the cytoplasm and mitochondria of rat liver. Biochem J. 1967 May;103(2):514–527. doi: 10.1042/bj1030514. [DOI] [PMC free article] [PubMed] [Google Scholar]

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