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. 1971 Jan;121(2):169–178. doi: 10.1042/bj1210169

Regulation of gluconeogenesis during exposure of young rats to hypoxic conditions

F J Ballard 1
PMCID: PMC1176552  PMID: 4330087

Abstract

1. Two-day-old rats were exposed at constant temperature to atmospheres containing air and nitrogen with the air content varied in steps from 100 to 0%. By using this system of graded hypoxia a comparison was made between rates of gluconeogenesis from lactate, serine and aspartate in the whole animal and the concentrations of several liver metabolites. 2. Gluconeogenesis, expressed as the percentage incorporation of labelled isotope into glucose plus glycogen, proceeds linearly for 30min when the animals are incubated in a normal air atmosphere, but is completely suppressed if the atmosphere is 100% nitrogen. 3. Preincubation of animals for between 5 and 30min under an atmosphere containing 19% air results in the attainment of a new steady state with respect to gluconeogenesis and hepatic concentrations of ATP, ADP, AMP, lactate, pyruvate, β-hydroxybutyrate and acetoacetate. 4. When lactate (100μmol), aspartate (20μmol) or serine (20μmol) was injected, it was shown that the more severe the hypoxia the greater the depression of gluconeogenesis. Under conditions when gluconeogenesis was markedly inhibited there were no changes in the degree of phosphorylation of hepatic adenine nucleotides, but free [NAD+]/[NADH] ratios fell in both cytosol and mitochondrial compartments of the liver cell. 5. Measurements of total liver NAD+ and NADH showed that the concentrations of these nucleotide coenzymes changed less with anoxia, in comparison with the concentration ratio of free coenzymes. 6. Calculations showed that the difference in NAD+–NADH redox potentials between mitochondrial and cytosol compartments increased with the severity of hypoxia. 7. From the constancy of the concentrations of adenine nucleotides it is concluded that liver of hypoxic rats can conserve ATP by lowering the rate of ATP utilization for gluconeogenesis. Gluconeogenesis may be regulated in turn by the changes in mitochondrial and cytosol redox state.

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Selected References

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

  1. Atkinson D. E., Walton G. M. Adenosine triphosphate conservation in metabolic regulation. Rat liver citrate cleavage enzyme. J Biol Chem. 1967 Jul 10;242(13):3239–3241. [PubMed] [Google Scholar]
  2. BALLARD F. J., OLIVER I. T. CARBOHYDRATE METABOLISM IN LIVER FROM FOETAL AND NEONATAL SHEEP. Biochem J. 1965 Apr;95:191–200. doi: 10.1042/bj0950191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BALLARD F. J., OLIVER I. T. Glycogen metabolism in embryonic chick and neonatal rat liver. Biochim Biophys Acta. 1963 Jun 4;71:578–588. doi: 10.1016/0006-3002(63)91130-2. [DOI] [PubMed] [Google Scholar]
  4. Ballard F. J. Adenine nucleotides and the adenylate kinase equilibrium in livers of foetal and newborn rats. Biochem J. 1970 Apr;117(2):231–235. doi: 10.1042/bj1170231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ballard F. J. Kinetic studies with cytosol and mitochondrial phosphoenolpyruvate carboxykinases. Biochem J. 1970 Dec;120(4):809–814. doi: 10.1042/bj1200809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Exton J. H., Park C. R. Control of gluconeogenesis in liver. II. Effects of glucagon, catecholamines, and adenosine 3',5'-monophosphate on gluconeogenesis in the perfused rat liver. J Biol Chem. 1968 Aug 25;243(16):4189–4196. [PubMed] [Google Scholar]
  7. LEHNINGER A. L., SUDDUTH H. C., WISE J. B. D-beta-Hydroxybutyric dehydrogenase of muitochondria. J Biol Chem. 1960 Aug;235:2450–2455. [PubMed] [Google Scholar]
  8. Philippidis H., Ballard F. J. The development of gluconeogenesis in rat liver. Effects of glucagon and ether. Biochem J. 1970 Nov;120(2):385–392. doi: 10.1042/bj1200385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Philippidis H., Ballard F. J. The development of gluconeogenesis in rat liver: experiments in vivo. Biochem J. 1969 Jul;113(4):651–657. doi: 10.1042/bj1130651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ross B. D., Hems R., Freedland R. A., Krebs H. A. Carbohydrate metabolism of the perfused rat liver. Biochem J. 1967 Nov;105(2):869–875. doi: 10.1042/bj1050869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Struck E., Ashmore J., Wieland O. Stimulierung der Gluconeogenese durch langkettige Fettsäuren und Glucagon. Biochem Z. 1965 Nov 5;343(1):107–110. [PubMed] [Google Scholar]
  12. Söling H. D., Willms B., Friedrichs D., Kleineke J. Regulation of gluconeogenesis by fatty acid oxidation in isolated perfused livers of non-starved rats. Eur J Biochem. 1968 Apr;4(3):364–372. doi: 10.1111/j.1432-1033.1968.tb00220.x. [DOI] [PubMed] [Google Scholar]
  13. WOLLENBERGER A., RISTAU O., SCHOFFA G. [A simple technic for extremely rapid freezing of large pieces of tissue]. Pflugers Arch Gesamte Physiol Menschen Tiere. 1960;270:399–412. [PubMed] [Google Scholar]
  14. 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]
  15. Williamson D. H., Veloso D., Ellington E. V., Krebs H. A. Changes in the concentrations of hepatic metabolites on administration of dihydroxyacetone or glycerol to starved rats and their relationship to the control of ketogenesis. Biochem J. 1969 Sep;114(3):575–584. doi: 10.1042/bj1140575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Williamson J. R., Browning E. T., Scholz R. Control mechanisms of gluconeogenesis and ketogenesis. I. Effects of oleate on gluconeogenesis in perfused rat liver. J Biol Chem. 1969 Sep 10;244(17):4607–4616. [PubMed] [Google Scholar]
  17. Williamson J. R., Browning E. T., Scholz R., Kreisberg R. A., Fritz I. B. Inhibition of fatty acid stimulation of gluconeogenesis by (+)-decanoylcarnitine in perfused rat liver. Diabetes. 1968 Apr;17(4):194–208. doi: 10.2337/diab.17.4.194. [DOI] [PubMed] [Google Scholar]
  18. Williamson J. R., Browning E. T., Thurman R. G., Scholz R. Inhibition of glucagon effects in perfused rat liver by (+)decanoylcarnitine. J Biol Chem. 1969 Sep 25;244(18):5055–5064. [PubMed] [Google Scholar]
  19. Williamson J. R., Scholz R., Browning E. T. Control mechanisms of gluconeogenesis and ketogenesis. II. Interactions between fatty acid oxidation and the citric acid cycle in perfused rat liver. J Biol Chem. 1969 Sep 10;244(17):4617–4627. [PubMed] [Google Scholar]

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