Phosphorylation and inactivation of HMG-CoA reductase at the AMP-activated protein kinase site in response to fructose treatment of isolated rat hepatocytes

FEBS Lett. 1992 Jul 13;306(1):59-62. doi: 10.1016/0014-5793(92)80837-7.

Abstract

We have previously shown that incubation of isolated hepatocytes with fructose leads to elevation of AMP and activation of the AMP-activated protein kinase. We now show that this treatment causes marked inactivation of HMG-CoA reductase. Using immunoprecipitation from the microsomal fraction of 32P-labelled cells, we also show that this treatment leads to a 2.6-fold increase in the phosphorylation of the 100 kDa subunit of HMG-CoA reductase. Successive digestion of this 32P-labelled subunit with cyanogen bromide and endoproteinase Lys-C confirmed that Ser-871, the site phosphorylated in cell-free assays by the AMP-activated protein kinase, was the only site phosphorylated under these conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoradiography
  • Binding Sites
  • Blotting, Western
  • Cells, Cultured
  • Cyanogen Bromide
  • Endopeptidases
  • Enzyme Activation
  • Fructose / pharmacology*
  • Hydroxymethylglutaryl CoA Reductases / metabolism*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Isoelectric Focusing
  • Liver / drug effects
  • Liver / enzymology*
  • Male
  • Metalloendopeptidases*
  • Phosphorylation
  • Precipitin Tests
  • Protein Kinases / metabolism*
  • Rats
  • Serine / metabolism

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Fructose
  • Serine
  • Hydroxymethylglutaryl CoA Reductases
  • Protein Kinases
  • Endopeptidases
  • Metalloendopeptidases
  • peptidyl-Lys metalloendopeptidase
  • Cyanogen Bromide