J. Lipid Res. Please sign the JLR Guestbook
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1194/jlr.M700208-JLR200 on October 27, 2007

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
M700208-JLR200v1
49/2/282    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shonsey, E. M.
Right arrow Articles by Renfrow, M. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shonsey, E. M.
Right arrow Articles by Renfrow, M. B.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Journal of Lipid Research, Vol. 49, 282-294, February 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

Inactivation of human liver bile acid CoA:amino acid N-acyltransferase by the electrophilic lipid, 4-hydroxynonenal

E. M. Shonsey1,{dagger}, S. M. Eliuk{dagger}, M. S. Johnson§, S. Barnes*,{dagger},**,§§, C. N. Falany{dagger}, V. M. Darley-Usmar§,{dagger}{dagger} and M. B. Renfrow*,§§

* Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294
{dagger} Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35294
§ Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294
** Comprehensive Cancer Center Mass Spectrometry Shared Facility, University of Alabama at Birmingham, Birmingham, AL 35294
{dagger}{dagger} Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL 35294
§§ University of Alabama Biomedical Fourier Transform-Ion Cyclotron Resonance Mass Spectrometry Laboratory, University of Alabama at Birmingham, Birmingham, AL 35294

Published, JLR Papers in Press, October 27, 2007.

1 To whom correspondence should be addressed. e-mail: eshonsey{at}uab.edu

The hepatic enzyme bile acid CoA:amino acid N-acyltransferase (BAT) catalyzes the formation of amino acid-conjugated bile acids. In the present study, protein carbonylation of BAT, consistent with modification by reactive oxygen species and their products, was increased in hepatic homogenates of apolipoprotein E knock-out mice. 4-Hydroxynonenal (4HNE), an electrophilic lipid generated by oxidation of polyunsaturated long-chain fatty acids, typically reacts with the amino acids Cys, His, Lys, and Arg to form adducts, some of which (Michael adducts) preserve the aldehyde (i.e., carbonyl) moiety. Because two of these amino acids (Cys and His) are members of the catalytic triad of human BAT, it was proposed that 4HNE would cause inactivation of this enzyme. As expected, human BAT (1.6 µM) was inactivated by 4HNE in a dose-dependent manner. To establish the sites of 4HNE's reaction with BAT, peptides from proteolysis of 4HNE-treated, recombinant human BAT were analyzed by peptide mass fingerprinting and by electrospray ionization-tandem mass spectrometry using a hybrid linear ion trap Fourier transform-ion cyclotron resonance mass spectrometer. The data revealed that the active-site His (His362) dose-dependently formed a 4HNE adduct, contributing to loss of activity, although 4HNE adducts on other residues may also contribute.

Supplementary key words coenzyme A • post-translational modifications • mass spectrometry


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Journal of Biological Chemistry 
 Molecular and Cellular Proteomics   ASBMB Today 
Copyright © 2008 by the American Society for Biochemistry and Molecular Biology.