Biochemistry and genetics of inherited disorders of peroxisomal fatty acid metabolism.
In humans, peroxisomes harbor a complex set of enzymes acting on various lipophilic carboxylic acids, organized in two basic pathways, alpha-oxidation and beta-oxidation; the latter pathway can also handle omega-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.
Van Veldhoven
Paul P
PP
Katholieke Universiteit Leuven, Department of Molecular Cell Biology, LIPIT, Campus Gasthuisberg, Herestraat, Leuven, Belgium. paul.vanveldhoven@med.kuleuven.be
D000818:Animals; D005227:Fatty Acids / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology; D010084:Oxidation-Reduction; D018901:Peroxisomal Disorders / Q000201:enzymology / Q000235:genetics*; D020675:Peroxisomes / Q000201:enzymology* / Q000378:metabolism; D010831:Phytanic Acid / Q000378:metabolism*
D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D010831:Phytanic Acid; C002844:pristanic acid