Peroxisomes in Humans: Metabolic Functions, Cross Talk with Other Organelles, and Pathophysiology of Peroxisomal Disorde
Peroxisomes play a crucial role in cellular metabolism as exemplified by the devastating consequences caused by deficiencies of one or more peroxisomal enzymes in humans. The major metabolic functions of peroxisomes in humans include fatty acid beta-oxida
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Peroxisomes in Humans: Metabolic Functions, Cross Talk with Other Organelles, and Pathophysiology of Peroxisomal Disorders Ronald J.A. Wanders, Sacha Ferdinandusse, and Hans R. Waterham
Abstract
Peroxisomes play a crucial role in cellular metabolism as exemplified by the devastating consequences caused by deficiencies of one or more peroxisomal enzymes in humans. The major metabolic functions of peroxisomes in humans include fatty acid beta-oxidation, etherphospholipid biosynthesis, fatty acid alpha-oxidation; glyoxylate detoxification, bile acid synthesis, L-pipecolic acid oxidation, and docosahexaenoic acid (DHA) formation. Except from the bile acids which are true metabolic end products of bile acid formation in the liver as generated in peroxisomes, all the other products of peroxisome metabolism are not true end products but require continued metabolism in other organelles to reach their final fate. This explains the crosstalk between peroxisomes and other subcellular organelles notably mitochondria and the endoplasmic reticulum. In this review we will discuss the metabolic functions of peroxisomes in humans and the crosstalk with other subcellular organelles. In addition we will discuss the pathophysiological consequences of genetic defects in peroxisome metabolism. Keywords
Peroxisomes • Peroxisomal disorders • Lipidomics • Lipids • Fatty acids • Mitochondria
R.J.A. Wanders (*) • S. Ferdinandusse • H.R. Waterham Laboratory Genetic Metabolic Diseases, Departments of Paediatrics and Clinical Chemistry, Emma Children’s Hospital, Academic Medical Center, 1105 Amsterdam, The Netherlands e-mail: [email protected] C. Brocard and A. Hartig (eds.), Molecular Machines Involved in Peroxisome Biogenesis and Maintenance, DOI 10.1007/978-3-7091-1788-0_3, # Springer-Verlag Wien 2014
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Introduction
Metabolism requires the catalysis of a large number of chemical reactions which allow cells to grow and reproduce, feed and excrete wastes, and move and communicate with their environment for the greater benefit of the cell itself whether part of a multicellular organism or not. This highly integrated network of chemical reactions is catalysed by enzymes that themselves are often organized in distinct multi-enzyme networks. An additional level of complexity is that, at least in higher eukaryotes, metabolism requires the participation of various membrane-bound compartments called organelles which each catalyse their own specific set of chemical reactions. The physical compartmentalization of the cytoplasm allows the coexistence of a diverse range of chemical micro-environments which are each precisely tailored to allow proper execution of a defined set of chemical reactions. There is constant communication and crosstalk between organelles which ensures an effective and cooperative division of metabolic labor. The fact that metabolism is divided over multiple subcellular organelles also requires the involvement of multiple transport proteins to allow exchange of metabolites between the
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