3-Hydroxy-3-methylglutaryl-coenzyme A reductase activity is inhibited by cholesterol and up-regulated by sitosterol in sitosterolemic fibroblasts

Sitosterolemia is an inherited recessive disease characterized by abnormally increased plasma and tissue plant sterol concentrations. Patients hyperabsorb sitosterol. In addition, hepatic, ileal, and mononuclear leukocyte 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-controllin...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of laboratory and clinical medicine 2000-02, Vol.135 (2), p.174-179
Main Authors: Honda, Akira, Salen, Gerald, Honda, Megumi, Batta, Ashok K., Tint, G.Stephen, Xu, Guorong, Chen, Thomas S., Tanaka, Naomi, Shefer, Sarah
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aorta, Thoracic
Arteriosclerosis - enzymology
Biological and medical sciences
Cells, Cultured
Cholesterol - pharmacology
Disorders of blood lipids. Hyperlipoproteinemia
Female
Fibroblasts - enzymology
Humans
Hydroxymethylglutaryl CoA Reductases - metabolism
Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology
Lipid Metabolism, Inborn Errors - blood
Lipid Metabolism, Inborn Errors - enzymology
Male
Medical sciences
Metabolic diseases
Reference Values
Sitosterols - blood
Sitosterols - pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Sitosterolemia is an inherited recessive disease characterized by abnormally increased plasma and tissue plant sterol concentrations. Patients hyperabsorb sitosterol. In addition, hepatic, ileal, and mononuclear leukocyte 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-controlling enzyme in the cholesterol biosynthetic pathway, is markedly suppressed in this disease. It is still controversial whether the down-regulation is due to accumulated sitosterol, but the effect of sitosterol on HMG-CoA reductase activity has not been studied in sitosterolemic tissues. To investigate whether sitosterol inhibits HMG-CoA reductase activity in sitosterolemia, we measured the enzyme activities in liver and cultured skin fibroblasts from patients. Hepatic HMG-CoA reductase activities in patients were decreased 76% (P
ISSN:0022-2143
1532-6543
DOI:10.1067/mlc.2000.104459