Glucagon and N6,O2′-dibutyryl adenosine 3′:5′-monophosphate inhibition of lipogenesis and phosphofructokinase activity of hepatocytes from meal-fed rats

Raymond S. Ochs, Robert A. Harris

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Glucagon and N6,O2′-dibutyryl adenosine 3′:5′-monophosphate (dibutyryl cyclic AMP) inhibit net glucose utilization, lactate plus pyruvate accumulation and fatty acid synthesis by isolated hepatocytes prepared from meal-fed rats. A crossover in the metabolite profile of the glycolytic intermediates occurs between fructose-6-phosphate and fructose-1,6-bisphosphate, suggesting either inhibition of phosphofructokinase or activation of fructose diphosphatase, or both. Direct assay of the enzymes in cell-free extracts of the hepatocytes indicates that dibutyryl cyclic AMP inhibits phosphofructokinase but has no effect upon fructose diphosphatase. The assay for phosphofructokinase was modified by the use of ITP in place of ATP for the phosphate donor as the ATP-linked assay is complicated by an apparent time-dependent activation of the enzyme. These findings strongly suggest that cyclic AMP inhibition of phosphofructokinase explains in part cyclic AMP inhibition of aerobic glycolysis and lipogenesis by rat liver hepatocytes.

Original languageEnglish (US)
Pages (from-to)504-511
Number of pages8
JournalLipids
Volume15
Issue number7
DOIs
StatePublished - Jul 1 1980

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Cell Biology

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