Characterization of the human omega-oxidation pathway for omega-hydroxy-very-long-chain fatty acids

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Robert-Jan SandersStephan Kemp

Abstract

Very-long-chain fatty acids (VLCFAs) have long been known to be degraded exclusively in peroxisomes via beta-oxidation. A defect in peroxisomal beta-oxidation results in elevated levels of VLCFAs and is associated with the most frequent inherited disorder of the central nervous system white matter, X-linked adrenoleukodystrophy. Recently, we demonstrated that VLCFAs can also undergo omega-oxidation, which may provide an alternative route for the breakdown of VLCFAs. The omega-oxidation of VLCFA is initiated by CYP4F2 and CYP4F3B, which produce omega-hydroxy-VLCFAs. In this article, we characterized the enzymes involved in the formation of very-long-chain dicarboxylic acids from omega-hydroxy-VLCFAs. We demonstrate that very-long-chain dicarboxylic acids are produced via two independent pathways. The first is mediated by an as yet unidentified, microsomal NAD(+)-dependent alcohol dehydrogenase and fatty aldehyde dehydrogenase, which is encoded by the ALDH3A2 gene and is deficient in patients with Sjögren-Larsson syndrome. The second pathway involves the NADPH-dependent hydroxylation of omega-hydroxy-VLCFAs by CYP4F2, CYP4F3B, or CYP4F3A. Enzyme kinetic studies show that oxidation of omega-hydroxy-VLCFAs occurs predominantly via ...Continue Reading

References

Dec 1, 1991·The Journal of Clinical Investigation·R K KunduG S Getz
Nov 1, 1989·Neurology·W B RizzoJ A Sgro
Mar 11, 1968·Archives of Biochemistry and Biophysics·K C Robbins
Jan 1, 1995·Advances in Experimental Medicine and Biology·L C HsuA Yoshida
Aug 28, 1998·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·L RuoccoR Rezzonico
Sep 5, 1998·The New England Journal of Medicine·I SinghS Pai
Nov 25, 1998·Molecular Aspects of Medicine·R J Wanders, J M Tager
Mar 24, 1999·Trends in Neurosciences·M Dubois-DalcqP Aubourg
Jul 12, 2003·Molecular Genetics and Metabolism·Fredoen ValianpourStephan Kemp
Apr 23, 1963·Biochimica Et Biophysica Acta·K WAKABAYASHI, N SHIMAZONO
Nov 25, 2003·The Journal of Pharmacology and Experimental Therapeutics·Fengyun XuDeanna L Kroetz
Oct 7, 2004·Molecular Genetics and Metabolism·R J A Wanders
Feb 18, 2005·Journal of Lipid Research·Robert-Jan SandersRonald J A Wanders
Jul 12, 2005·Human Genomics·Vasilis Vasiliou, Daniel W Nebert
Mar 21, 2006·The Journal of Biological Chemistry·Robert-Jan SandersRonald J A Wanders
Oct 14, 2006·Pflügers Archiv : European journal of physiology·Ronald J A WandersHans R Waterham
Dec 5, 2006·The Journal of Biological Chemistry·Mei-Hui HsuEric F Johnson

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Citations

Jun 19, 2010·Journal of Lipid Research·Paul P Van Veldhoven
Aug 21, 2013·Biochimica Et Biophysica Acta·Bernadette Breiden, Konrad Sandhoff
Feb 12, 2014·Human Molecular Genetics·Olga PougovkinaVincent C J de Boer
Nov 6, 2014·Pharmacogenetics and Genomics·Maria L AlvarellosTeri E Klein
Jun 10, 2015·Proceedings of the National Academy of Sciences of the United States of America·Yusuke OhnoAkio Kihara
Aug 23, 2016·Expert Opinion on Orphan Drugs·William B Rizzo
Apr 23, 2015·The International Journal of Biochemistry & Cell Biology·Alla B SalminaLyudmila L Petrova
Jun 23, 2011·Dermato-endocrinology·William B Rizzo
Jun 18, 2016·Nature Reviews. Endocrinology·Stephan KempMarc Engelen
Oct 19, 2010·Evidence-based Complementary and Alternative Medicine : ECAM·Young Jin MoonMarilyn E Morris
Oct 11, 2015·Biochimica Et Biophysica Acta·Myriam Baes, Paul P Van Veldhoven
Oct 3, 2017·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Yusuke Ohno
Dec 16, 2010·The FEBS Journal·Ronald J A WandersStephan Kemp
May 11, 2013·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Angela CintolesiRamon Gonzalez
Jul 3, 2021·International Journal of Molecular Sciences·Christos Chinopoulos
Aug 13, 2021·Journal of Proteome Research·Amelie S Lotz-HavlaSøren W Gersting
Aug 29, 2021·Pharmacology & Therapeutics·Martin RiecanOndrej Kuda
Jan 7, 2009·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Robert-Jan SandersRonald J A Wanders

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Adrenoleukodystrophy

Adrenoleukodystrophy (ALD), the most frequent peroxisomal disorder, is an X-linked disorder caused by a defect in the metabolism of long chain fatty acids leading to demyelination, neurodegeneration, and death. Here is the latest research.