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. 1967 Aug;46(8):1283–1296. doi: 10.1172/JCI105621

Studies in the Ketosis of Fasting*

Daniel W Foster 1,†
PMCID: PMC297130  PMID: 16695917

Abstract

A series of experiments was performed during the induction of starvation ketosis and in the acute reversal of the ketotic state. In contrast to the predictions of two widely held theories of ketogenesis, control of acetoacetate production by the liver appeared to be unrelated to changes in fatty acid mobilization from the periphery, fatty acid oxidation, fatty acid synthesis, or the acetyl coenzyme A concentration in the liver.

Ketosis of fasting was shown to be reversible within 5 minutes by the injection of glucose or insulin. This effect was due to a prompt cessation of acetoacetate production by the liver. The possibility is raised that the ketosis of fasting is due to a direct activation of acetoacetate-synthesizing enzymes secondary to a starvation-induced depression of insulin secretion by the pancreas.

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Selected References

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

  1. AMATRUDA T. T., Jr, ENGEL F. L. The role of the endocrine glands in ketosis. I. The ketosis of fasting. Yale J Biol Med. 1959 Apr;31(5):303–323. [PMC free article] [PubMed] [Google Scholar]
  2. BEATTY C. H., PETERSON R. D., BOCEK R. M., WEST E. S. THE EFFECT OF INSULIN AND DEPRIVATION OF FOOD ON METABOLISM OF ACETOACETIC ACID BY MUSCLE. J Biol Chem. 1964 Jul;239:2106–2109. [PubMed] [Google Scholar]
  3. BORTZ W. M., LYNEN F. THE INHIBITION OF ACETYL COA CARBOXYLASE BY LONG CHAIN ACYL COA DERIVATIVES. Biochem Z. 1963 Aug 14;337:505–509. [PubMed] [Google Scholar]
  4. BRAGDON J. H., GORDON R. S., Jr Tissue distribution of C14 after the intravenous injection of labeled chylomicrons and unesterified fatty acids in the rat. J Clin Invest. 1958 Apr;37(4):574–578. doi: 10.1172/JCI103640. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. BRESSLER R. The biochemistry of ketosis. Ann N Y Acad Sci. 1963 Mar 5;104:735–752. doi: 10.1111/j.1749-6632.1963.tb17705.x. [DOI] [PubMed] [Google Scholar]
  6. DOLE V. P. A relation between non-esterified fatty acids in plasma and the metabolism of glucose. J Clin Invest. 1956 Feb;35(2):150–154. doi: 10.1172/JCI103259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. FEIGENBAUM A. S., FISHER H. Changes in fatty acid composition in nutritional fatty degeneration of the liver. 1. Effect of starvation. Br J Nutr. 1963;17:31–37. doi: 10.1079/bjn19630004. [DOI] [PubMed] [Google Scholar]
  8. FRITZ I. B. Factors influencing the rates of long-chain fatty acid oxidation and synthesis in mammalian systems. Physiol Rev. 1961 Jan;41:52–129. doi: 10.1152/physrev.1961.41.1.52. [DOI] [PubMed] [Google Scholar]
  9. FRITZ I. B., KAPLAN E. Effects of glucose on fatty acid oxidation by diaphragms from normal and alloxan-diabetic fed and starved rats. Am J Physiol. 1960 Jan;198:39–44. doi: 10.1152/ajplegacy.1960.198.1.39. [DOI] [PubMed] [Google Scholar]
  10. GOODMAN D. S. Preparation of human serum albumin free of long-chain fatty acids. Science. 1957 Jun 28;125(3261):1296–1297. doi: 10.1126/science.125.3261.1296. [DOI] [PubMed] [Google Scholar]
  11. KALNITSKY G., TAPLEY D. F. A sensitive method for estimation of oxaloacetate. Biochem J. 1958 Sep;70(1):28–34. doi: 10.1042/bj0700028. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. KREBS H. Biochemical aspects of ketosis. Proc R Soc Med. 1960 Feb;53:71–80. [PMC free article] [PubMed] [Google Scholar]
  13. LYON J. B., Jr, BLOOM W. L. The use of furfural for the determination of acetone bodies in biological fluids. Can J Biochem Physiol. 1958 Oct;36(10):1047–1056. [PubMed] [Google Scholar]
  14. McCALLA C., GATES H. S., Jr, GORDON R. S., Jr C1402 Excretion after the intravenous administration of albumin-bound palmitate-1-C14 to intact rats. Arch Biochem Biophys. 1957 Oct;71(2):346–351. doi: 10.1016/0003-9861(57)90044-9. [DOI] [PubMed] [Google Scholar]
  15. OCHOA S., STERN J. R., SCHNEIDER M. C. Enzymatic synthesis of citric acid. II. Crystalline condensing enzyme. J Biol Chem. 1951 Dec;193(2):691–702. [PubMed] [Google Scholar]
  16. OPIE L. H., EVANS J. R., SHIPP J. C. EFFECT OF FASTING ON GLUCOSE AND PALMITATE METABOLISM OF PERFUSED RAT HEART. Am J Physiol. 1963 Dec;205:1203–1208. doi: 10.1152/ajplegacy.1963.205.6.1203. [DOI] [PubMed] [Google Scholar]
  17. SAIFER A., GERSTENFELD S. The photometric microdetermination of blood glucose with glucose oxidase. J Lab Clin Med. 1958 Mar;51(3):448–460. [PubMed] [Google Scholar]
  18. SCOW R. O., CHERNICK S. S., BRINLEY M. S. HYPERLIPEMIA AND KETOSIS IN THE PREGNANT RAT. Am J Physiol. 1964 Apr;206:796–804. doi: 10.1152/ajplegacy.1964.206.4.796. [DOI] [PubMed] [Google Scholar]
  19. SCOW R. O., CHERNICK S. S. Hormonal control of protein and fat metabolism in the pancreatectomized rat. Recent Prog Horm Res. 1960;16:497–545. [PubMed] [Google Scholar]
  20. SIPERSTEIN M. D., FAGAN V. M. Studies on the relationship between glucose oxidation and intermediary metabolism. I. The influence of glycolysis on the synthesis of cholesterol and fatty acid in normal liver. J Clin Invest. 1958 Aug;37(8):1185–1195. doi: 10.1172/JCI103708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. SIPERSTEIN M. D., FAGAN V. M. Studies on the relationship between glucose oxidation and intermediary metabolism. II. The role of glucose oxidation in lipogenesis in diabetic rat liver. J Clin Invest. 1958 Aug;37(8):1196–1201. doi: 10.1172/JCI103709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. SIPERSTEIN M. D. Inter-relationships of glucose and lipid metabolism. Am J Med. 1959 May;26(5):685–702. doi: 10.1016/0002-9343(59)90228-1. [DOI] [PubMed] [Google Scholar]
  23. SRERE P. A., SEUBERT W., LYNEN F. Palmityl coenzyme A deacylase. Biochim Biophys Acta. 1959 Jun;33(2):313–319. doi: 10.1016/0006-3002(59)90118-0. [DOI] [PubMed] [Google Scholar]
  24. Srere P. A., Foster D. W. On the proposed relation of citrate enzymes to fatty acid synthesis and ketosis in starvation. Biochem Biophys Res Commun. 1967 Mar 9;26(5):556–561. doi: 10.1016/0006-291x(67)90101-5. [DOI] [PubMed] [Google Scholar]
  25. TEPPERMAN J., TEPPERMAN H. M. Effects of antecedent food intake pattern on hepatic lipogenesis. Am J Physiol. 1958 Apr;193(1):55–64. doi: 10.1152/ajplegacy.1958.193.1.55. [DOI] [PubMed] [Google Scholar]
  26. TROUT D. L., ESTES E. H., Jr, FRIEDBERG S. J. Titration of free fatty acids of plasma: a study of current methods and a new modification. J Lipid Res. 1960 Apr;1:199–202. [PubMed] [Google Scholar]
  27. TUBBS P. K. INHIBITION OF CITRATE FORMATION BY LONG-CHAIN ACYL THIOESTERS OF COENZYME A AS A POSSIBLE CONTROL MECHANISM IN FATTY ACID BIOSYNTHESIS. Biochim Biophys Acta. 1963 Oct 22;70:608–609. doi: 10.1016/0006-3002(63)90804-7. [DOI] [PubMed] [Google Scholar]
  28. Tubbs P. K., Garland P. B. Variations in tissue contents of coenzyme A thio esters and possible metabolic implications. Biochem J. 1964 Dec;93(3):550–557. doi: 10.1042/bj0930550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. WALKER P. G. A colorimetric method for the estimation of acetoacetate. Biochem J. 1954 Dec;58(4):699–704. doi: 10.1042/bj0580699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. WHITE J. E., ENGEL F. L. Lipolytic action of corticotropin on rat adipose tissue in vitro. J Clin Invest. 1958 Nov;37(11):1556–1563. doi: 10.1172/JCI103748. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. WIELAND O., WEISS L. INHIBITION OF CITRATE-SYNTHASE BY PALMITYL-COENZYME A. Biochem Biophys Res Commun. 1963 Sep 10;13:26–31. doi: 10.1016/0006-291x(63)90156-6. [DOI] [PubMed] [Google Scholar]
  32. WIELAND O., WEISS L. Increase in liver acetyl-coenzyme A during ketosis. Biochem Biophys Res Commun. 1963 Feb 18;10:333–339. doi: 10.1016/0006-291x(63)90534-5. [DOI] [PubMed] [Google Scholar]
  33. WILLIAMSON D. H., MELLANBY J., KREBS H. A. Enzymic determination of D(-)-beta-hydroxybutyric acid and acetoacetic acid in blood. Biochem J. 1962 Jan;82:90–96. doi: 10.1042/bj0820090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wieland O., Weiss L., Eger-Neufeldt I. Enzymatic regulation of liver acetyl-CoA metabolism in relation to ketogenesis. Adv Enzyme Regul. 1964;2:85–99. doi: 10.1016/s0065-2571(64)80007-8. [DOI] [PubMed] [Google Scholar]

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