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. 1967 Mar;102(3):942–951. doi: 10.1042/bj1020942

The rate of gluconeogenesis from various precursors in the perfused rat liver

B D Ross 1, R Hems 1, H A Krebs 1
PMCID: PMC1270348  PMID: 16742514

Abstract

1. The rates of gluconeogenesis from many precursors have been measured in the perfused rat liver and, for comparison, in rat liver slices. All livers were from rats starved for 48hr. Under optimum conditions the rates in perfused liver were three to five times those found under optimum conditions in slices. 2. Rapid gluconeogenesis (rates of above 0·5μmole/g./min.) were found with lactate, pyruvate, alanine, serine, proline, fructose, dihydroxyacetone, sorbitol, xylitol. Unexpectedly other amino acids, notably glutamate and aspartate, and the intermediates of the tricarboxylic acid cycle (with the exception of oxaloacetate), reacted very slowly and were not readily removed from the perfusion medium, presumably because of permeability barriers which prevent the passage of highly charged negative ions. Glutamine and asparagine formed glucose more readily than the corresponding amino acids. 3. Glucagon increased the rate of gluconeogenesis from lactate and pyruvate but not from any other precursor tested. This occurred when the liver was virtually completely depleted of glycogen. Two sites of action of glucagon must therefore be postulated: one concerned with mobilization of liver glycogen, the other with the promotion of gluconeogenesis. Sliced liver did not respond to glucagon. 4. Pyruvate and oxaloacetate formed substantial quantities of lactate on perfusion, which indicates that the reducing power provided in the cytoplasm was in excess of the needs of gluconeogenesis. 5. Values for the content of intermediary metabolites of gluconeogenesis in the perfused liver are reported. The values for most intermediates rose on addition of lactate. 6. The rates of gluconeogenesis from lactate and pyruvate were not affected by wide variations of the lactate/pyruvate ratio in the perfusion medium.

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Selected References

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

  1. Exton J. H., Jefferson L. S., Jr, Butcher R. W., Park C. R. Gluconeogenesis in the perfused liver. The effects of fasting, alloxan diabetes, glucagon, epinephrine, adenosine 3',5'-monophosphate and insulin. Am J Med. 1966 May;40(5):709–715. doi: 10.1016/0002-9343(66)90151-3. [DOI] [PubMed] [Google Scholar]
  2. GARLAND P. B., RANDLE P. J. A rapid enzymatic assay for glycerol. Nature. 1962 Dec 8;196:987–988. doi: 10.1038/196987a0. [DOI] [PubMed] [Google Scholar]
  3. HASTINGS A. B., TENG C. T., NESBETT F. B., SINEX F. M. Studies on carbohydrate metabolism in rat liver slices. I. The effect of cations in the media. J Biol Chem. 1952 Jan;194(1):69–81. [PubMed] [Google Scholar]
  4. Hems R., Ross B. D., Berry M. N., Krebs H. A. Gluconeogenesis in the perfused rat liver. Biochem J. 1966 Nov;101(2):284–292. doi: 10.1042/bj1010284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. KREBS H. A., BELLAMY D. The interconversion of glutamic acid and aspartic acid in respiring tissues. Biochem J. 1960 Jun;75:523–529. doi: 10.1042/bj0750523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. KREBS H. A., HEMS R., GASCOYNE T. RENAL GLUCONEOGENESIS. IV. GLUCONEOGENESIS FROM SUBSTRATE COMBINATIONS. Acta Biol Med Ger. 1963;11:607–615. [PubMed] [Google Scholar]
  7. KREBS H. A., SPEAKE R. N., HEMS R. ACCELERATION OF RENAL GLUCONEOGENESIS BY KETONE BODIES AND FATTY ACIDS. Biochem J. 1965 Mar;94:712–720. doi: 10.1042/bj0940712. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Krebs H. A., Notton B. M., Hems R. Gluconeogenesis in mouse-liver slices. Biochem J. 1966 Dec;101(3):607–617. doi: 10.1042/bj1010607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. LOEFFLER G., WIELAND O. [An isotope method for the enzymatic determination of oxalacetate]. Biochem Z. 1963;336:447–454. [PubMed] [Google Scholar]
  10. MANCHESTER K. L., YOUNG F. G. The effect of insulin in vitro on the accumulation of amino acids by isolated rat diaphragm. Biochem J. 1960 Jun;75:487–495. doi: 10.1042/bj0750487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. MILLER L. L., BURKE W. T., HAFT D. E. Interrelations in amino acid and carbohydrate metabolism; studies of the nitrogen sparing action of carbohydrate with the isolated perfused rat liver. Fed Proc. 1955 Sep;14(3):707–716. [PubMed] [Google Scholar]
  12. SCHIMASSEK H. [Metabolites of carbohydrate metabolism in the isolated perfused rat liver]. Biochem Z. 1963;336:460–467. [PubMed] [Google Scholar]
  13. SOKAL J. E., SARCIONE E. J. FAILURE OF PHYSIOLOGICAL CONCENTRATIONS OF EPINEPHRINE TO AFFECT GLYCOGEN-LEVELS IN THE ISOLATED RAT LIVER. Nature. 1964 Nov 28;204:881–883. doi: 10.1038/204881a0. [DOI] [PubMed] [Google Scholar]
  14. Sokal J. E. Effect of glucagon on gluconeogenesis by the isolated perfused rat liver. Endocrinology. 1966 Mar;78(3):538–548. doi: 10.1210/endo-78-3-538. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Williamson J. R., Garcia A., Renold A. E., Cahill G. F., Jr Studies on the perfused rat liver. I. Effects of glucagon and insulin on glucose metabolism. Diabetes. 1966 Mar;15(3):183–187. doi: 10.2337/diab.15.3.183. [DOI] [PubMed] [Google Scholar]

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