Regulation of three key enzymes in cholesterol metabolism by phosphorylation/dephosphorylation.
AUTOR(ES)
Scallen, T J
RESUMO
Our laboratories have investigated the role of phosphorylation/dephosphorylation in the regulation of three key enzymes in cholesterol metabolism. 3-Hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase (EC 1.1.1.34), the major regulatory enzyme in cholesterol biosynthesis, is inhibited by phosphorylation. Acyl-CoA:cholesterol O-acyltransferase (ACATase; EC 2.3.1.26) and cholesterol 7 alpha-hydroxylase (EC 1.14.13.7), key regulatory enzymes in the utilization of cholesterol, are activated by phosphorylation. In view of these results, we propose that short-term regulation of the concentration of intracellular unesterified cholesterol is achieved by a coordinate phosphorylation/dephosphorylation of these three enzymes. For example, if cholesterol enters the liver cell, HMG-CoA reductase would be inhibited by phosphorylation and biosynthesis of cholesterol would be reduced; however, reactions utilizing cholesterol would be activated, due to the phosphorylation of ACATase and cholesterol 7 alpha-hydroxylase. Thus, the phosphorylation/dephosphorylation of these three enzymes provides an elegant short-term mechanism for the homeostasis of intracellular unesterified cholesterol.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=393848Documentos Relacionados
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