Document Detail

Attenuation of Slc27a5 gene expression followed by LC/MS measurement of bile acid re-conjugation using metabolomics and a stable isotope tracer strategy.
MedLine Citation:
PMID:  21819150     Owner:  NLM     Status:  Publisher    
The purpose of this study was to evaluate the use of high resolution LC/MS together with metabolomics and D4-cholic acid (D4-CA) as a metabolic tracer to measure the metabolism and reconjugation of bile acids (BAs) in vitro and in vivo. Metabolic tracers are very important because allow for the direct detection (substrate-to-product) of small and significant biological perturbations which may not be apparent when monitoring 'static' endogenous levels of particular metabolites. Slc27a5, also known as fatty acid transport protein 5 (FATP5), is the hepatic BA-CoA ligase involved in re-conjugating BAs during enterohepatic BA recycling. Using Slc27a5-cKD mice, silencing of ~90% gene expression was achieved followed by reduction in the re-conjugation of D4-CA to D4-taurocholic acid (D4-TCA), as well as other conjugated BA metabolites in plasma (p= 0.0031). The method described allowed a rapid measure of many D4 and endogenous BA. Analysis of bile resulted in the detection of 39 BA metabolites from a 13 min analytical run. Finally, the utilization of a novel high resolution mass spectrometry method in combination with metabolomics and a stable isotope metabolic tracer allowed for the detection of targeted and untargeted BAs following silencing of the Slc27a5 gene in primary hepatocytes and in mice.
Jose M Castro-Perez; Thomas P Roddy; Vinit Shah; Sheng-Ping Wang; Xuesong Ouyang; Anthony Ogawa; David G McLaren; Marija Tadin-Strapps; Michael J Robinson; Steven R Bartz; Brandon Ason; Ying Chen; Stephen F Previs; Kenny K Wong; Rob J Vreeken; Douglas G Johns; Brian K Hubbard; Thomas Hankemeier; Lyndon Mitnaul
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-8-8
Journal Detail:
Title:  Journal of proteome research     Volume:  -     ISSN:  1535-3907     ISO Abbreviation:  -     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-8-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101128775     Medline TA:  J Proteome Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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