Hormonal control of ketogenesis. Biochemical considerations

Arch Intern Med. 1977 Apr;137(4):495-501.


A two-site, bihormonal concept for the control of ketone body production is proposed. Thus, ketosis is viewed as the result of increased mobilization of free fatty acids from adipose tissue (site 1) to the liver (site 2), coupled with simultaneous enhancement of the liver's capacity to convert these substrates into acetoacetic and beta-hydroxybutyric acids. The former event is believed to be triggered by a fall in plasma insulin levels while the latter is considered to be effected primarily by the concomitant glucagon excess characteristic of the ketotic state. Although the precise mechanism whereby elevation of the circulating [glucagon]:[insulin] ratio stimulates hepatic ketogenic potential is not known, activation of the carnitine acyltransferase reaction, the first step in the oxidation of fatty acids, is an essential feature. Two prerequisites for this metabolic adaptation in liver appear to be an elevation in its carnitine content and depletion of its glycogen stores. Despite present limitations the model (evolved mainly from rat studies) provides a framework for the description of various types of clinical ketosis in biochemical terms and may be useful for future studies.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetoacetates / biosynthesis
  • Acidosis / etiology*
  • Adipose Tissue / metabolism
  • Alcoholism / metabolism
  • Animals
  • Carnitine / metabolism
  • Carnitine Acyltransferases / metabolism
  • Diabetic Ketoacidosis / etiology
  • Fatty Acids, Nonesterified / metabolism
  • Glucagon / metabolism*
  • Humans
  • Hydroxybutyrates / biosynthesis
  • Insulin / metabolism*
  • Ketosis / etiology*
  • Ketosis / metabolism
  • Lipid Mobilization
  • Liver / metabolism
  • Liver Glycogen / metabolism
  • Models, Biological
  • Rats
  • Starvation / metabolism


  • Acetoacetates
  • Fatty Acids, Nonesterified
  • Hydroxybutyrates
  • Insulin
  • Liver Glycogen
  • Glucagon
  • Carnitine Acyltransferases
  • Carnitine