Activation of HMG-CoA reductase by microsomal phosphatase

K R Feingold,M H Wiley,A H Moser,S R Lear,M D Siperstein

doi:10.1016/s0022-2275(20)37997-9

Abstract

HMG-CoA reductase activity can be modulated by a reversible phosphorylation-dephosphorylation with the phosphorylated form of the enzyme being inactive and the dephosphorylated form, active. Phosphatases from diverse sources, including cytosol, have been shown to dephosphorylate and activate HMG-CoA reductase. The present study demonstrates phosphatase activity capable of activating HMG-CoA reductase that is associated with purified microsomes. The incubation of microsomes at 37 degrees C for 40 min results in a twofold stimulation of HMG-CoA reductase activity, and this stimulation is blocked by sodium fluoride or phosphate. The ability of microsomes to increase HMG-CoA reductase activity occurs regardless of whether microsomes are prepared by ultracentrifugation or calcium precipitation. Additionally, phosphatases capable of activating HMG-CoA reductase are present in both the smooth and rough endoplasmic reticulum. Freeze-thawing does not prevent microsomes from activating HMG-CoA reductase but preincubation results in a significant decrease in the ability of microsomes to increase HMG-CoA reductase activity. Thus, the present study demonstrates that purified liver microsomes contain phosphatase activity capable of activating HMG-CoA reductase.

Highlights

HMG-CoA reductase activity can be modulated by a reversible phosphorylation-dephosphorylationwith the phosphorylated form of the enzyme being inactive and the dephosphorylated form, active
T h e results in Table 1 demonstrate that purified microsomes contain a phosphatase that is capable of activating HMG-CoA reductase
It should be noted that isocitrate dehydrogenase is present in cytosol and the absence of this enzyme in purified microsomes further suggests the absence of cytosolic contamination of the microsomal fraction

Summary

Introduction

HMG-CoA reductase activity can be modulated by a reversible phosphorylation-dephosphorylationwith the phosphorylated form of the enzyme being inactive and the dephosphorylated form, active. Phosphatases from diverse sources, including cytosol, have been shown to dephosphorylate and activate HMG-CoA reductase. T h e present study demonstrates phosphatase activity capable of activating HMGCoA reductase that is associated with purified microsomes. T h e incubation of microsomes at 37°C for 40 min results in a twofold stimulation of HMG-CoA reductase activity, and this stimulation is blocked by sodium fluoride o r phosphate. Phosphatases capable of activating HMG-CoA reductase are present in both the smooth and rough endoplasmic reticulum. Freeze-thawing does not prevent microsomes from activating HMG-CoA reductase but preincubation results in a significant decrease in the ability of microsomes to increase HMG-CoA reductase activityM the present study demonstrates that purified liver microsomes contain phosphatase activity capable of activating HMG-CoA reductase.-Feingold, K.

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