J. Lipid Res.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on May 1, 2005

Papers In Press, published online ahead of print February 16, 2005
J. Lipid Res., doi:10.1194/jlr.M400510-JLR200
This Article
Right arrow Full Text (Accepted Manuscript)
Right arrow All Versions of this Article:
M400510-JLR200v1
46/5/1001    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
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 HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sanders, R.-J.
Right arrow Articles by Wanders, R. J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sanders, R.-J.
Right arrow Articles by Wanders, R. J. A.
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?

Submitted on December 22, 2004
Revised on February 9, 2005
Accepted on February 10, 2005

Evidence for two enzymatic pathways for omega-oxidation of docosanoic acid in rat liver microsomes

Robert-Jan Sanders, Rob Ofman, Fredoen Valianpour, Stephan Kemp, and Ronald J. A. Wanders

Laboratory Genetic Metabolic Diseases, Academic Medical Center, Amsterdam 1105 AZ

Corresponding Author: r.j.wanders{at}amc.uva.nl

In this paper we studied the omega -oxidation of docosanoic acid (C22:0) in rat liver microsomes. C22:0 and 22-hydroxy-docosanoic acid (omega -hydroxy-C22:0) were used as substrates and the reaction products were analyzed by electrospray ionization mass spectrometry. In the presence of NADPH, omega -oxidation of C22:0 did not only produce the hydroxylated product, omega -hydroxy-C22:0, but also the dicarboxylic acid of C22:0 (C22:0-DCA). When rat liver microsomes were incubated with omega -hydroxy-C22:0 either in the presence of NAD+ or NADPH, C22:0-DCA was formed readily. Formation of C22:0-DCA either from C22:0 or omega -hydroxy-C22:0 with NADPH as cofactor was inhibited strongly by miconazole and disulfiram, whereas no inhibition was found with NAD+ as cofactor. Furthermore, omega -oxidation of C22:0 was reduced significantly when molecular oxygen was depleted. The high sensitivity towards the more specific P450 inhibitors ketoconazole and 17-octadecynoic acid suggests that hydroxylation of C22:0 and omega -hydroxy-C22:0 may be catalyzed by one or more cytochrome P450 hydroxylases belonging to the CYP4A and/ or 4F subfamily. This study demonstrates that C22:0 is a substrate for the omega -oxidation system in rat liver microsomes and that the product of the first hydroxylation step, omega -hydroxy-C22:0, may undergo further oxidation via two distinct pathways driven by NAD+ or NADPH, respectively.


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?


This article has been cited by other articles:


Home page
 FASEB J.Home page
R.-J. Sanders, R. Ofman, G. Dacremont, R. J. A. Wanders, and S. Kemp
Characterization of the human {omega}-oxidation pathway for {omega}-hydroxy-very-long-chain fatty acids
FASEB J, June 1, 2008; 22(6): 2064 - 2071.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
S. Leekumjorn, Y. Wu, A. K. Sum, and C. Chan
Experimental and Computational Studies Investigating Trehalose Protection of HepG2 Cells from Palmitate-Induced Toxicity
Biophys. J., April 1, 2008; 94(7): 2869 - 2883.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
H.-Q. Yin, M. Kim, J.-H. Kim, G. Kong, M.-O. Lee, K.-S. Kang, B.-I. Yoon, H.-L. Kim, and B.-H. Lee
Hepatic Gene Expression Profiling and Lipid Homeostasis in Mice Exposed to Steatogenic Drug, Tetracycline
Toxicol. Sci., November 1, 2006; 94(1): 206 - 216.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
F. Xu, V. Y. Ng, D. L. Kroetz, and P. R. O. de Montellano
CYP4 Isoform Specificity in the {omega}-Hydroxylation of Phytanic Acid, a Potential Route to Elimination of the Causative Agent of Refsum's Disease
J. Pharmacol. Exp. Ther., August 1, 2006; 318(2): 835 - 839.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R.-J. Sanders, R. Ofman, M. Duran, S. Kemp, and R. J. A. Wanders
{omega}-Oxidation of Very Long-chain Fatty Acids in Human Liver Microsomes: IMPLICATIONS FOR X-LINKED ADRENOLEUKODYSTROPHY
J. Biol. Chem., May 12, 2006; 281(19): 13180 - 13187.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. A. McDonough, K. L. Kavanagh, D. Butler, T. Searls, U. Oppermann, and C. J. Schofield
Structure of Human Phytanoyl-CoA 2-Hydroxylase Identifies Molecular Mechanisms of Refsum Disease
J. Biol. Chem., December 9, 2005; 280(49): 41101 - 41110.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. A. K. Westin, M. C. Hunt, and S. E. H. Alexson
The Identification of a Succinyl-CoA Thioesterase Suggests a Novel Pathway for Succinate Production in Peroxisomes
J. Biol. Chem., November 18, 2005; 280(46): 38125 - 38132.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 All ASBMB Journals   Journal of Biological Chemistry 
 Molecular and Cellular Proteomics   ASBMB Today 
Copyright © 2005 by the American Society for Biochemistry and Molecular Biology.