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

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.