3-Hydroxy-3-methylglutaryl coenzyme A reductase: regulation of enzymatic activity by phosphorylation and dephosphorylation.
نویسندگان
چکیده
The activity of microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) [mevalonate:NADP+ oxidoreductase (CoA-acylating); EC 1.1.1.34] was inhibited by ATP+Mg2+. Inactivation of HMG-CoA reductase by ATP+Mg2+ was dependent on time, temperature, and ATP concentration. Incubation of microsomal HMG-CoA reductase with [gamma-32P]ATP+Mg2+ was associated with a reciprocal increase in [32P]protein-bound radioactivity and a decrease in enzymatic activity. Incubation of 32P-labeled microsomal HMG-CoA reductase with a partially purified cytosolic phosphatase resulted in a time-dependent reciprocal release of [32P]protein-bound radioactivity and reactivation of enzyme activity. Phosphorylation of HMG-CoA reductase was confirmed by immunoprecipitation of partially purified [gamma-32P]-ATP+Mg2+-inactivated microsomal HMG-CoA reductase with a reductase-specific antiserum. Sodium dodecyl sulfate electrophoresis of the [gamma-32P]immunoprecipitate revealed that the 32P radioactivity was located in the electrophoretic position of HMG-CoA reductase. These results established that the reversible inactivation of HMG-CoA reductase by ATP+Mg2+ was due to covalent modification of the enzyme by a phosphorylation-dephosphorylation reaction sequence. The existence of HMG-CoA reductase in interconvertible active and inactive forms provides a mechanism for the rapid short-term regulation of the pathway for cholesterol biosynthesis.
منابع مشابه
Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase by reversible phosphorylation-dephosphorylation.
متن کامل
Evidence for phosphorylation/dephosphorylation of rat liver acyl-CoA:cholesterol acyltransferase.
Acyl-coenzyme A:cholesterol O-acyltransferase (ACATase; EC 2.3.1.26) is a membrane-bound microsomal enzyme that catalyzes the formation of long-chain fatty-acyl cholesterol esters in rat liver and other tissues. This enzyme is important in regulating the concentration of unesterified cholesterol in the cell. Having recently demonstrated that rat liver 3-hydroxy-3-methylglutaryl-coenzyme A reduc...
متن کاملReversible inactivation-reactivation of 3-hydroxy-3-methylglutaryl coenzyme A reductase of rat intestine.
3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in the ileum of rats was inactivated by Mg2+-ATP and reversibly reactivated by cytoplasmic activator from the liver. The mevalonate kinase reaction was presumably not involved in this inactivation. Studies of nucleotide specificity for the inactivation revealed that ATP was most effective in the reaction among the nucleotides tested. In ...
متن کاملIn vivo modulation of rat liver 3-hydroxy-3-methylglutaryl-coenzyme A reductase, reductase kinase, and reductase kinase kinase by mevalonolactone.
It has been previously demonstrated that the enzymic activity of rat liver 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase; EC 1.1.1.34) is modulated in vitro and in vivo by a bicyclic cascade system involving reversible phosphorylation of HMG-CoA reductase and reductase kinase. In the present study, administration of mevalonolactone to rats caused a rapid inhibition of HMG-C...
متن کامل3-Hydroxy-3-methylglutaryl coenzyme A reductase activity in the human gastrointestinal tract.
Activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.34) was measured in intestinal mucosa of the human gastrointestinal tract. Activity was highest in gastric mucosa (18.2 pmol per mg per min) and there was a constant low level in the small bowel and colon (approximately 10 pmol per mg per min). Phosphorylation/dephosphorylation modulation of intestinal reductase activity was ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Proceedings of the National Academy of Sciences of the United States of America
دوره 75 8 شماره
صفحات -
تاریخ انتشار 1978