Activation of HMG-CoA reductase by microsomal phosphatase

• Published in: Journal of lipid research Vol. 24; no. 3; pp. 290 - 296
• Main Authors: Feingold, K R, Wiley, M H, Moser, A H, Lear, S R, Siperstein, M D
• Format: Journal Article
• Language: English
• Published: United States Elsevier 01.03.1983
• Subjects: Animals; Enzyme Activation; Freezing; Hydroxymethylglutaryl CoA Reductases - metabolism; hydroxymethylglutaryl-CoA reductase; liver; microsomes; Microsomes, Liver - enzymology; phosphatases; Phosphoric Monoester Hydrolases - metabolism; Rats; Rats, Inbred Strains; Sodium Chloride - pharmacology; Sodium Fluoride - pharmacology; Time Factors
• ISSN: 0022-2275; 1539-7262
• DOI: 10.1016/S0022-2275(20)37997-9

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.