Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • 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
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Immune Environment in Glioblastoma (Feb 2023)
    • Korsmeyer Award 25th Anniversary Collection (Jan 2023)
    • Aging (Jul 2022)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Research letters
    • Letters to the editor
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Research letters
  • Letters to the editor
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Version history
  • Article usage
  • Citations to this article

Advertisement

Free access | 10.1172/JCI108952

Multicompartmental Analysis of Cholesterol Metabolism in Man: CHARACTERIZATION OF THE HEPATIC BILE ACID AND BILIARY CHOLESTEROL PRECURSOR SITES

Charles C. Schwartz, Mones Berman, Z. R. Vlahcevic, L. Gregg Halloran, Daniel H. Gregory, and Leon Swell

Division of Gastroenterology, Department of Medicine, Veterans Administration Hospital, Richmond, Virginia 23249

Division of Gastroenterology, Department of Surgery, Veterans Administration Hospital, Richmond, Virginia 23249

Medical College of Virginia, Richmond, Virginia 23249

Laboratory of Theoretical Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20014

Find articles by Schwartz, C. in: JCI | PubMed | Google Scholar

Division of Gastroenterology, Department of Medicine, Veterans Administration Hospital, Richmond, Virginia 23249

Division of Gastroenterology, Department of Surgery, Veterans Administration Hospital, Richmond, Virginia 23249

Medical College of Virginia, Richmond, Virginia 23249

Laboratory of Theoretical Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20014

Find articles by Berman, M. in: JCI | PubMed | Google Scholar

Division of Gastroenterology, Department of Medicine, Veterans Administration Hospital, Richmond, Virginia 23249

Division of Gastroenterology, Department of Surgery, Veterans Administration Hospital, Richmond, Virginia 23249

Medical College of Virginia, Richmond, Virginia 23249

Laboratory of Theoretical Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20014

Find articles by Vlahcevic, Z. in: JCI | PubMed | Google Scholar

Division of Gastroenterology, Department of Medicine, Veterans Administration Hospital, Richmond, Virginia 23249

Division of Gastroenterology, Department of Surgery, Veterans Administration Hospital, Richmond, Virginia 23249

Medical College of Virginia, Richmond, Virginia 23249

Laboratory of Theoretical Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20014

Find articles by Halloran, L. in: JCI | PubMed | Google Scholar

Division of Gastroenterology, Department of Medicine, Veterans Administration Hospital, Richmond, Virginia 23249

Division of Gastroenterology, Department of Surgery, Veterans Administration Hospital, Richmond, Virginia 23249

Medical College of Virginia, Richmond, Virginia 23249

Laboratory of Theoretical Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20014

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

Division of Gastroenterology, Department of Medicine, Veterans Administration Hospital, Richmond, Virginia 23249

Division of Gastroenterology, Department of Surgery, Veterans Administration Hospital, Richmond, Virginia 23249

Medical College of Virginia, Richmond, Virginia 23249

Laboratory of Theoretical Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20014

Find articles by Swell, L. in: JCI | PubMed | Google Scholar

Published February 1, 1978 - More info

Published in Volume 61, Issue 2 on February 1, 1978
J Clin Invest. 1978;61(2):408–423. https://doi.org/10.1172/JCI108952.
© 1978 The American Society for Clinical Investigation
Published February 1, 1978 - Version history
View PDF
Abstract

The present report has presented the first clear evidence in man for the existence of specific hepatic cholesterol precursor sites associated with the formation and secretion of bile acids and biliary cholesterol. These hepatic compartments derive virtually all their cholesterol from newly synthesized and lipoprotein free cholesterol. The model which is presented was formulated on current concepts of cholesterol metabolism in man and is concerned, at this initial stage, with the elucidation of the bile acid and biliary cholesterol compartments. The complexity of cholesterol metabolism in man necessitated an initial approach that would minimize the number of inputs of cholesterol into the system, allow for the sampling of several cholesterol compartments, and permit the simultaneous labeling of newly synthesized cholesterol and preformed cholesterol. To achieve these objectives, we studied the patient with a total bile fistula. Six patients were administered simultaneously pulse injections of labeled mevalonic acid and [14C]cholesterol. The qualitative features of the specific activity time course curves after labeled mevalonic acid revealed no precursor-product relationship between bile acid, biliary cholesterol, and plasma free cholesterol. The peak specific activity of the bile acids was reached in approximately 100 min and was higher than the biliary cholesterol, which was higher than the plasma free cholesterol. The plasma free cholesterol specific activity became higher than the other lipids after 12 h and remained higher throughout the period of study. Similar related observations were made with [14C]cholesterol. The data were then subjected to simulation analysis and modeling using the SAAM-27 computer program. Computer least-square fits of the data were obtained after the model was evolved. During the model development, the least number of compartments and transport pathways were introduced consistent with a good fit of the data. Of particular importance was the constraint that the model fit the data obtained from both [14C]cholesterol and labeled mevalonic acid. The same parameter values were used to fit the data from both tracers. The fluxes arrived at in the model indicate that 31% and 20%, respectively, of the cholesterol input into the bile acid and biliary cholesterol precursor sites were derived directly from the newly synthesized hepatic cholesterol. The remainder had its origin predominantly from lipoprotein free cholesterol. Plasma esterified cholesterol (as free) made a small contribution (11%) to the bile acid compartment. Similarly, 10% of the biliary cholesterol arose from an unknown hepatic site.

The present report has provided the basis for a new procedure for studying in vivo cholesterol metabolism in man. Examination of the derived cholesterol flux rates between the compartments suggests the presence of an important mechanism regulating the partitioning of lipoprotein free cholesterol between the bile acid and biliary cholesterol precursor sites. Aberrations in the proportioning of precursor cholesterol between these sites could be a causative factor precipitating the excessive secretion of biliary cholesterol and the production of lithogenic bile.

Browse pages

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

icon of scanned page 408
page 408
icon of scanned page 409
page 409
icon of scanned page 410
page 410
icon of scanned page 411
page 411
icon of scanned page 412
page 412
icon of scanned page 413
page 413
icon of scanned page 414
page 414
icon of scanned page 415
page 415
icon of scanned page 416
page 416
icon of scanned page 417
page 417
icon of scanned page 418
page 418
icon of scanned page 419
page 419
icon of scanned page 420
page 420
icon of scanned page 421
page 421
icon of scanned page 422
page 422
icon of scanned page 423
page 423
Version history
  • Version 1 (February 1, 1978): No description

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Share this article
  • 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 © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts