Activation of HMG-CoA reductase by microsomal phosphatase.
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.
D000818:Animals; D004789:Enzyme Activation; D005615:Freezing; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D008862:Microsomes, Liver / Q000201:enzymology*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000494:pharmacology; D012969:Sodium Fluoride / Q000494:pharmacology; D013997:Time Factors
D012965:Sodium Chloride; D012969:Sodium Fluoride; D006903:Hydroxymethylglutaryl CoA Reductases; D010744:Phosphoric Monoester Hydrolases