HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 11, 9802-9812, March 18, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/11/9802    most recent M413362200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Foulon, V. Articles by Casteels, M. Search for Related Content PubMed PubMed Citation Articles by Foulon, V. Articles by Casteels, M. Social Bookmarking                      What's this?

Breakdown of 2-Hydroxylated Straight Chain Fatty Acids via Peroxisomal 2-Hydroxyphytanoyl-CoA Lyase

A REVISED PATHWAY FOR THE -OXIDATION OF STRAIGHT CHAIN FATTY ACIDS^*

Veerle Foulon, Mieke Sniekers, Els Huysmans, Stanny Asselberghs, Vincent Mahieu, Guy P. Mannaerts, Paul P. Van Veldhoven¶, and Minne Casteels||

From the Afdeling Farmacologie, Departement Celbiologie, Katholieke Universiteit Leuven, Campus Gasthuisberg, 3000 Leuven, Belgium

2-Hydroxyfatty acids, constituents of brain cerebrosides and sulfatides, were previously reported to be degraded by an -oxidation system, generating fatty acids shortened by one carbon atom. In the current study we used labeled and unlabeled 2-hydroxyoctadecanoic acid to reinvestigate the degradation of this class of lipids. Both in intact and broken cell systems formate was identified as a main reaction product. Furthermore, the generation of an n–1 aldehyde was demonstrated. In permeabilized rat hepatocytes and liver homogenates, studies on cofactor requirements revealed a dependence on ATP, CoA, Mg²⁺, thiamine pyrophosphate, and NAD⁺. Together with subcellular fractionation data and studies on recombinant enzymes, this led to the following picture. In a first step, the 2-hydroxyfatty acid is activated to an acyl-CoA; subsequently, the 2-hydroxy fatty acyl-CoA is cleaved by 2-hydroxyphytanoyl-CoA lyase, to formyl-CoA and an n–1 aldehyde. The severe inhibition of formate generation by oxythiamin treatment of intact fibroblasts indicates that cleavage through the thiamine pyrophosphate-dependent 2-hydroxyphytanoyl-CoA lyase is the main pathway for the degradation of 2-hydroxyfatty acids. The latter protein was initially characterized as an essential enzyme in the peroxisomal -oxidation of 3-methyl-branched fatty acids such as phytanic acid. Our findings point to a new role for peroxisomes in mammals, i.e. the breakdown of 2-hydroxyfatty acids, at least the long chain 2-hydroxyfatty acids. Most likely, the more abundant very long chain 2-hydroxyfatty acids are degraded in a similar manner.

Received for publication, November 29, 2004 , and in revised form, January 6, 2005.

^* This work was supported by Geconcerteerde Onderzoeksacties van de Vlaamse Gemeenschap Grants GOA 99/03-09 and GOA 2004/08, Fonds voor Wetenschappelijk Onderzoek-Vlaanderen Grant G.0115.02, and European Union project RDDPT, Grant QLG3-CT-2002-00696. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Both authors contributed equally to this work.

Supported by a fellowship from the Fonds voor Wetenschappelijk Onderzoek-Vlaanderen.

^¶ To whom correspondence may be addressed: Departement Celbiologie, Afdeling Farmacologie, Faculteit Geneeskunde, Katholieke Universiteit Leuven, Herestraat 49, Box 601, 3000 Leuven, Belgium. Tel.: 32-16-345802; Fax: 32-16-345699; E-mail: paul.vanveldhoven{at}med.kuleuven.ac.be. || To whom correspondence may be addressed: Departement Celbiologie, Afdeling Farmacologie, Faculteit Geneeskunde, Katholieke Universiteit Leuven, Herestraat 49, Box 601, 3000 Leuven, Belgium. Tel.: 32-16-345816; Fax: 32-16-345699; E-mail: minne.casteels{at}med.kuleuven.ac.be.

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

This article has been cited by other articles:

				S. J Huybrechts, P. P Van Veldhoven, I. Hoffman, R. Zeevaert, R. de Vos, P. Demaerel, M. Brams, J. Jaeken, M. Fransen, and D. Cassiman Identification of a novel PEX14 mutation in Zellweger syndrome BMJ Case Reports, January 22, 2009; 2009(jan21_1): bcr0720080503 - bcr0720080503. [Abstract] [Full Text]

				S J Huybrechts, P P Van Veldhoven, I Hoffman, R Zeevaert, R de Vos, P Demaerel, M Brams, J Jaeken, M Fransen, and D Cassiman Identification of a novel PEX14 mutation in Zellweger syndrome J. Med. Genet., June 1, 2008; 45(6): 376 - 383. [Abstract] [Full Text] [PDF]

				L. Hulshagen, O. Krysko, A. Bottelbergs, S. Huyghe, R. Klein, P. P. Van Veldhoven, P. P. De Deyn, R. D'Hooge, D. Hartmann, and M. Baes Absence of Functional Peroxisomes from Mouse CNS Causes Dysmyelination and Axon Degeneration J. Neurosci., April 9, 2008; 28(15): 4015 - 4027. [Abstract] [Full Text] [PDF]

				G. H. Borchert, M. Giggey, F. Kolar, T. M. Wong, P. H. Backx, and P. V. Escriba 2-Hydroxyoleic acid affects cardiomyocyte [Ca2+]i transient and contractility in a region-dependent manner Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1948 - H1955. [Abstract] [Full Text] [PDF]

				R. Alemany, O. Vogler, S. Teres, C. Egea, C. Baamonde, F. Barcelo, C. Delgado, K. H. Jakobs, and P. V. Escriba Antihypertensive action of 2-hydroxyoleic acid in SHRs via modulation of the protein kinase A pathway and Rho kinase J. Lipid Res., August 1, 2006; 47(8): 1762 - 1770. [Abstract] [Full Text] [PDF]