Lipid metabolism in peroxisomes: enzymology, functions and dysfunctions of the fatty acid alpha- and beta-oxidation systems in humans.
Peroxisomes are subcellular organelles present in virtually all eukaryotic cells catalysing a number of indispensable functions in cellular metabolism. The importance of peroxisomes in man is stressed by the existence of an expanding group of genetic diseases in which there is an impairment in one or more peroxisomal functions. One of the major functions of peroxisomes concerns their role in lipid metabolism, which includes: (i) fatty acid betaoxidation; (ii) ether phospholipid synthesis; (iii) fatty acid alpha-oxidation; and (iv) isoprenoid biosynthesis. In this paper, we review the current state of knowledge concerning the peroxisomal fatty acid alpha- and beta-oxidation systems with particular emphasis on the enzymes involved and the various disorders of fatty acid oxidation in peroxisomes. We also pay attention to the fact that some of the metabolites that accumulate as the result of a defect in peroxisomal alpha- and/or beta-oxidation are activators of members of the family of nuclear receptors, including peroxisome-proliferator-activated receptor alpha.
Wanders
R J
RJ
University of Amsterdam, Academic Medical Center, Department of Clinical Chemistry, The Netherlands.
van Grunsven
E G
EG
Jansen
G A
GA
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000378:metabolism; D000101:Acetyl-CoA C-Acetyltransferase / Q000378:metabolism; D042962:Acyl-CoA Oxidase; D002467:Cell Nucleus / Q000378:metabolism; D004746:Enoyl-CoA Hydratase / Q000378:metabolism; D005227:Fatty Acids / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D050356:Lipid Metabolism; D008954:Models, Biological; D010088:Oxidoreductases / Q000378:metabolism; D018901:Peroxisomal Disorders / Q000378:metabolism; D020675:Peroxisomes / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D005227:Fatty Acids; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C002844:pristanic acid; D010088:Oxidoreductases; D015094:3-Hydroxyacyl CoA Dehydrogenases; D042962:Acyl-CoA Oxidase; D000101:Acetyl-CoA C-Acetyltransferase; D004746:Enoyl-CoA Hydratase