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Quantification of statin effects on hepatic cholesterol synthesis by transient 13C-flux analysis

Paper ID Volume ID Publish Year Pages File Format Full-Text
31789 44838 2009 18 PDF Available
Title
Quantification of statin effects on hepatic cholesterol synthesis by transient 13C-flux analysis
Abstract

The present work is the first to deal with the determination of cholesterol synthesis rates in primary rat hepatocytes using transient 13C-flux analysis. The effects of statins on cholesterol biosynthesis and central carbon fluxes were quantified at a therapeutic concentration of 50 nM atorvastatin using carbon-labeled glutamine. The flux through the cholesterol pathway decreased from 0.27 to 0.08 mmol/lcv h in response to the administration of the hypolipidemic drug. Isotopic steady state was reached within 4 h in the central carbon metabolism but not in the cholesterol pathway, regardless of whether atorvastatin was administered or not. Marked channeling was observed for the symmetrical tricarboxylic acid cycle intermediates, succinate and fumarate. Non-stationary 13C-based flux identification delivers both intracellular fluxes and intermediate levels, which was for the first time utilized for investigating systems-level effects of the administered drug by quantifying the flux control of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase.

Keywords
Metabolic flux analysis; Non-stationary 13C-labeling; Mammalian cells; Hepatic metabolism; HMG-CoA reductase; Atorvastatin; Intracellular metabolite concentrations; Metabolic control analysis
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Quantification of statin effects on hepatic cholesterol synthesis by transient 13C-flux analysis
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Publisher
Database: Elsevier - ScienceDirect
Journal: Metabolic Engineering - Volume 11, Issues 4–5, July–September 2009, Pages 292–309
Authors
, , , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us