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INTRODUCTION TO PEROXISOME BIOLOGY AND METABOLISM

Peroxisomes are single membrane-bound organelles present in virtually all eukaryotic cells that number between hundreds to a few thousand per cell. Peroxisomes appear on electron micrographs as spherical organelles (Fig. 157-1) and contain a dense proteinaceous matrix composed of over 50 enzymes. Peroxisomes are involved in a diverse list of metabolic processes, but the most well characterized are the enzymatic β-oxidation of very-long-chain fatty acids and other substrates, biosynthesis of plasmalogens and bile acids, α-oxidation of branched chain fatty acids (phytanic acid), and glyoxylate and lysine degradation. Furthermore, catalase and other antioxidant enzymes in peroxisomes play a role in regulating the cellular redox balance. Peroxisomes form through the concerted action of an evolutionarily conserved protein machinery encoded by the PEX genes (Table 157-1). The PEX gene products orchestrate a process of de novo peroxisome biogenesis that begins with designation of membrane compartment, derived from the endoplasmic reticulum. In addition to de novo peroxisome biogenesis, peroxisomes can form from existing peroxisomes through fission, and recent studies have suggested that fission may play at least as important a role in creating new peroxisomes as de novo biogenesis.

Figure 157-1

Electron micrograph of human liver hepatocytes showing peroxisomes, spherical electron dense granules approximately 500 nm in diameter. Also seen are the mitochondria and glycogen granules. (Used with permission from Milton Finegold, MD, Professor of Pathology and Immunology, Baylor College of Medicine.)

TABLE 157-1HUMAN GENES INVOLVED IN PEROXISOMAL BIOGENESIS

Peroxisome biogenesis begins with membrane derived from the endoplasmic reticulum. The membrane designation step underlying de novo biogenesis of peroxisomes is a process that requires the PEX3, PEX16, and PEX19 genes (Fig. 157-2A). While PEX3 and PEX16 proteins associate with the early peroxisome membrane, PEX19 is a cytosolic protein involved in targeting membrane proteins to the peroxisome. The resulting pre-peroxisomal vesicle is populated with additional peroxisomal membrane proteins by PEX19 protein and others, and eventually becomes competent to import matrix enzymes. The import of peroxisomal enzymes starts with the translation of these proteins on free ribosomes in the cytosol. The translated proteins ...

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