Biochemistry and genetics of inherited disorders of peroxisomal fatty acid metabolism[S]
- Katholieke Universiteit Leuven, Department of Molecular Cell Biology, LIPIT, Campus Gasthuisberg, Herestraat, Leuven, Belgium
- 1To whom correspondence should be addressed. e-mail: paul.vanveldhoven{at}med.kuleuven.be
Abstract
In humans, peroxisomes harbor a complex set of enzymes acting on various lipophilic carboxylic acids, organized in two basic pathways, α-oxidation and β-oxidation; the latter pathway can also handle ω-oxidized compounds. Some oxidation products are crucial to human health (primary bile acids and polyunsaturated FAs), whereas other substrates have to be degraded in order to avoid neuropathology at a later age (very long-chain FAs and xenobiotic phytanic acid and pristanic acid). Whereas total absence of peroxisomes is lethal, single peroxisomal protein deficiencies can present with a mild or severe phenotype and are more informative to understand the pathogenic factors. The currently known single protein deficiencies equal about one-fourth of the number of proteins involved in peroxisomal FA metabolism. The biochemical properties of these proteins are highlighted, followed by an overview of the known diseases.
- adrenoleukodystrophy
- ATP binding cassette-transporter
- carnitine
- cholestanoic acid
- chondrodysplasia
- dicarboxylic acids
- docosahexaenoic acid
- lignoceric acid
- phytanic acid
- phytol
- Refsum
- Zellweger
Footnotes
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- Abbreviations:
- 2OH-FA
- 2-hydroxy FA
- ABC
- ATP binding cassette
- ACSL
- long-chain acyl-CoA synthetase
- ACSVL
- very long-chain acyl-CoA synthetase
- CMC
- critical micellar concentration
- PTS
- peroxisome targeting signal
- PMP
- peroxisomal integral membrane protein
- RCDP
- rhizomelic chondrodysplasia punctata
- SCP
- sterol carrier protein
- SLC
- solute carrier
- SLS
- Sjögren-Larsson syndrome
- THCA
- 3α,7α,12α-trihydroxycholestanoic acid
- TPP
- thiamine-pyrophosphate
- VLC
- very long-chain
- ZS
- Zellweger syndrome
- X-ALD
- X-linked adrenoleukodystrophy
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Financial support was received from the Flemish government (Geconcerteerde Onderzoeksacties 2004/08), Fonds voor Wetenschappelijk Onderzoek-Vlaanderen (G.0721.10N), and K.U.Leuven (OT/09/045).
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↵[S] The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of two figures.
- Received February 5, 2010.
- Revision received June 17, 2010.
- Copyright © 2010 by the American Society for Biochemistry and Molecular Biology, Inc.
