Peroxisomes and peroxisomal disorders.

During their classic studies on the Separation of lysosomes by centrifugation of rat liver homogenates, De Duve and bis group (1) observed that certain oxidative enzymes, such äs Z)-amino acid oxidase and uric acid oxidase wbich produce hydrogen peroxide, and catalase which attacks hydrogen peroxide, were always found in a discrete fraction which could be separated from lysosomes and mitochondria. These enzymes were believed to be associated with special organelles called peroxisomes and shown to be identical to the organelles first described by Rhodin (2) äs microbodies in 1954. Peroxisomes are mainly spherical organelles bounded by a trilaminar unit membrane and containing a fme granulär matrix. It is believed that peroxisomal proteins are formed on the endoplasmic reticulum and that peroxisomes are then produced by a budding process. Peroxisomes are never formed de novo and a cell must contain at least one single peroxisome. It is now well established that peroxisomes exhibit important functions in mammalian lipid and amino acid metabolism. These functions include Steps in the biosynthesis of plasmalogens and bile acids and fatty acid ß-oxidation, particularly those of very long chain fatty acids. The interest in peroxisomes has been greatly stimulated by two lines of investigations, i. e. the discovery of the remarkable proliferative effect of several hypolipidaemic drugs such äs clofibrate on hepatic peroxisomes, and the recognition of several genetic human disorders in which peroxisomes are either totally absent or abnormal. In 1965 Zellweger (3) in Iowa City and Bowen (4) at Johns Hopkins described certain neonates, which develop characteristic Symptoms such äs muscular hypotonia, seizures with neonatal onset, psychomotor retardation, craniofacial dysmorphism and ocular involvement. Similar disorders in 5 siblings were described by Passarge & McAdams (5), demonstrating disorders in brain, liver and kidney, who coined the term cerebro-hepato-renal syndrome. In 1969 Opitz (6) proposed the eponym Zellweger syndrome for the case first described at Iowa City in honour of his former teacher. In 1973 Goldfischer and coworkers (7) demonstrated that patients with Zellweger syndrome show a reduced number or absence of peroxisomes. Studies on the peroxisomal fatty acid oxidase System helped to clarify the pathogenesis of Zellweger syndrome. The enzymes involved in the peroxisomal ß-oxidation System were purified and characterized by Hashimoto (8). In principle both the starting compound and the product of ß-oxidation are identical in peroxisomes and mitochondria, but the enzymes involved are totally different. The peroxisomal pathway, which is most important for …