Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Version history
  • Article usage
  • Citations to this article

Advertisement

Research Article Free access | 10.1172/JCI113218

In vivo regulation of human mononuclear leukocyte 3-hydroxy-3-methylglutaryl coenzyme A reductase. Decreased enzyme catalytic efficiency in familial hypercholesterolemia.

P W Stacpoole, D M Bridge, I M Alvarez, R B Goldberg, and H J Harwood Jr

Department of Medicine (Division of Endocrinology and Metabolism), University of Florida, College of Medicine, Gainesville 32610.

Find articles by Stacpoole, P. in: PubMed | Google Scholar

Department of Medicine (Division of Endocrinology and Metabolism), University of Florida, College of Medicine, Gainesville 32610.

Find articles by Bridge, D. in: PubMed | Google Scholar

Department of Medicine (Division of Endocrinology and Metabolism), University of Florida, College of Medicine, Gainesville 32610.

Find articles by Alvarez, I. in: PubMed | Google Scholar

Department of Medicine (Division of Endocrinology and Metabolism), University of Florida, College of Medicine, Gainesville 32610.

Find articles by Goldberg, R. in: PubMed | Google Scholar

Department of Medicine (Division of Endocrinology and Metabolism), University of Florida, College of Medicine, Gainesville 32610.

Find articles by Harwood, H. in: PubMed | Google Scholar

Published November 1, 1987 - More info

Published in Volume 80, Issue 5 on November 1, 1987
J Clin Invest. 1987;80(5):1401–1408. https://doi.org/10.1172/JCI113218.
© 1987 The American Society for Clinical Investigation
Published November 1, 1987 - Version history
View PDF
Abstract

3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMG CoA reductase) controls the rate of cholesterol biosynthesis and is itself modulated through feedback suppression by internalized low density lipoprotein (LDL) cholesterol. We measured HMG CoA reductase protein concentration and microsomal enzyme activity in freshly isolated mononuclear leukocytes from normal individuals and patients with heterozygous or homozygous familial hypercholesterolemia (FH). Reductase protein concentration was similar in normal and heterozygous subjects, but was over twofold elevated in patients with homozygous FH. Reductase protein concentration was inversely related to LDL receptor status. Total activity and catalytic efficiency of reductase, however, were decreased in heterozygous and homozygous FH patients. The decrease in catalytic efficiency was not due to enzyme phosphorylation or thiol-disulfide formation. Reduction of plasma cholesterol concentration over 2 h by plasmapheresis increased reductase activity, the degree of which was directly proportional to the LDL-receptor status of the subjects. Decreased HMG CoA reductase activity and catalytic efficiency in mononuclear leukocytes and perhaps other cells in FH may represent a fundamental abnormality in the regulation of this enzyme independent of that induced by the LDL-receptor defect and may provide new insight into the control of cholesterol metabolism in FH.

Browse pages

Click on an image below to see the page. View PDF of the complete article

icon of scanned page 1401
page 1401
icon of scanned page 1402
page 1402
icon of scanned page 1403
page 1403
icon of scanned page 1404
page 1404
icon of scanned page 1405
page 1405
icon of scanned page 1406
page 1406
icon of scanned page 1407
page 1407
icon of scanned page 1408
page 1408
Version history
  • Version 1 (November 1, 1987): No description

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Abstract
  • Version history
Advertisement
Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts