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Breakdown of 2-hydroxylated straight chain fatty acids via peroxisomal 2-hydroxyphytanoyl-CoA lyase: a revised pathway for the alpha-oxidation of straight chain fatty acids.
J Biol Chem. 2005 Mar 18; 280(11):9802-12.JB

Abstract

2-Hydroxyfatty acids, constituents of brain cerebrosides and sulfatides, were previously reported to be degraded by an alpha-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, Mg(2+), 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 alpha-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.

Authors+Show Affiliations

Afdeling Farmacologie, Departement Celbiologie, Katholieke Universiteit Leuven, Campus Gasthuisberg, 3000 Leuven, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15644336

Citation

Foulon, Veerle, et al. "Breakdown of 2-hydroxylated Straight Chain Fatty Acids Via Peroxisomal 2-hydroxyphytanoyl-CoA Lyase: a Revised Pathway for the Alpha-oxidation of Straight Chain Fatty Acids." The Journal of Biological Chemistry, vol. 280, no. 11, 2005, pp. 9802-12.
Foulon V, Sniekers M, Huysmans E, et al. Breakdown of 2-hydroxylated straight chain fatty acids via peroxisomal 2-hydroxyphytanoyl-CoA lyase: a revised pathway for the alpha-oxidation of straight chain fatty acids. J Biol Chem. 2005;280(11):9802-12.
Foulon, V., Sniekers, M., Huysmans, E., Asselberghs, S., Mahieu, V., Mannaerts, G. P., Van Veldhoven, P. P., & Casteels, M. (2005). Breakdown of 2-hydroxylated straight chain fatty acids via peroxisomal 2-hydroxyphytanoyl-CoA lyase: a revised pathway for the alpha-oxidation of straight chain fatty acids. The Journal of Biological Chemistry, 280(11), 9802-12.
Foulon V, et al. Breakdown of 2-hydroxylated Straight Chain Fatty Acids Via Peroxisomal 2-hydroxyphytanoyl-CoA Lyase: a Revised Pathway for the Alpha-oxidation of Straight Chain Fatty Acids. J Biol Chem. 2005 Mar 18;280(11):9802-12. PubMed PMID: 15644336.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Breakdown of 2-hydroxylated straight chain fatty acids via peroxisomal 2-hydroxyphytanoyl-CoA lyase: a revised pathway for the alpha-oxidation of straight chain fatty acids. AU - Foulon,Veerle, AU - Sniekers,Mieke, AU - Huysmans,Els, AU - Asselberghs,Stanny, AU - Mahieu,Vincent, AU - Mannaerts,Guy P, AU - Van Veldhoven,Paul P, AU - Casteels,Minne, Y1 - 2005/01/11/ PY - 2005/1/13/pubmed PY - 2005/4/26/medline PY - 2005/1/13/entrez SP - 9802 EP - 12 JF - The Journal of biological chemistry JO - J Biol Chem VL - 280 IS - 11 N2 - 2-Hydroxyfatty acids, constituents of brain cerebrosides and sulfatides, were previously reported to be degraded by an alpha-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, Mg(2+), 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 alpha-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. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/15644336/Breakdown_of_2_hydroxylated_straight_chain_fatty_acids_via_peroxisomal_2_hydroxyphytanoyl_CoA_lyase:_a_revised_pathway_for_the_alpha_oxidation_of_straight_chain_fatty_acids_ DB - PRIME DP - Unbound Medicine ER -