Defects in mitochondrial and peroxisomal fatty acid oxidation

Abstract

This chapter describes the disorders of mitochondrial and peroxisomal fatty acid oxidation (FAO). In order to provide the necessary background, a brief update is provided on the enzymology and characteristics of the peroxisomal and mitochondrial FAO systems. The important difference between peroxisomes and mitochondria is the involvement of carnitine in the two systems. In mitochondria, carnitine plays an essential role in the import of FAs from the cytosolic space into the mitochondrial matrix. In mitochondria, carnitine is involved in the transfer of long-chain fatty acids (Fas) across the mitochondrial membrane via the concerted action of carnitine palmitoyl transferase 1 (CPT1), the mitochondrial CACT, and carnitine palmitoyl transferase 2 (CPT2). From a physiological point of view, the most important difference between the mitochondrial and peroxisomal beta-oxidation systems is that the two systems have different substrates specificities. The realization that the peroxisomal system handles a distinct set of substrates has largely come from studies on a rare genetic disease, called the cerebro-hepato-renal syndrome of Zellweger, in short Zellweger syndrome (ZS). The chapter also explains disorders of peroxisomal FA alpha-oxidation.