[Peroxisomal beta-oxidation]

Abstract

In animal cells peroxisomes as well as mitochondria are capable of degrading lipids via beta-oxidation. Nevertheless, there are important differences between the two systems. 1) The peroxisomal and mitochondrial beta-oxidation enzymes are different proteins. 2) Peroxisomal beta-oxidation does not degrade fatty acids completely but acts as a chain-shortening system, catalyzing only a limited number of beta-oxidation cycles. 3) Peroxisomal beta-oxidation is not coupled to oxidative phosphorylation and is thus less efficient than mitochondrial beta-oxidation as far as energy conservation is concerned. 4) Peroxisomal beta-oxidation is not regulated by malonyl-CoA and--as a consequence--by feeding as opposed to starvation. Peroxisomes are responsible for the beta-oxidation of very long chain (> C20) fatty acids, dicarboxylic fatty acids, 2-methyl-branched fatty acids, prostaglandins, leukotrienes, and the carboxyl side chains of certain xenobiotics and of the bile acid intermediates di- and trihydroxycoprostanic acids. Mitochondria oxidize mainly long (C16-C20) chain fatty acids, which--because of their abundance--constitute a major source of metabolic fuel. The first step in peroxisomal beta-oxidation is catalyzed by two acyl-CoA oxidases in extrahepatic tissues and by three acyl-CoA oxidases in liver, each enzyme having its own substrate specificity. Palmitoyl-CoA oxidase and pristanoyl-CoA oxidase are found in liver and extrahepatic tissues. The former enzyme oxidizes the CoA esters of straight chain fatty acids, dicarboxylic fatty acids and prostaglandins; the latter enzyme oxidizes the CoA esters of branched fatty acids but also shows some activity towards straight chain and dicarboxylic fatty acids. Hepatic peroxisomes contain a third acyl-CoA oxidase, trihydroxycoprostanoyl-CoAA oxidase, which oxidizes the CoA esters of the bile acid intermediates di- an trihydroxycoprostanic acids. Treatment of rodents with a number of structurally diverse compounds called peroxisome proliferators, results in the proliferation of peroxisomes, especially in liver, and in the induction of the hepatic peroxisomal beta-oxidation enzymes except pristanoyl-CoA oxidase and trihydroxycoprostanoyl-CoA oxidase. There exist several inborn errors, in which peroxisomal beta-oxidation is deficient. These diseases are characterized by severe neurological symptoms. The biochemical findings in these diseases confirm the function of peroxisomal beta-oxidation as described above.