Nonalcoholic steatosis and steatohepatitis. III. Peroxisomal beta-oxidation, PPAR alpha, and steatohepatitis.
Peroxisomes are involved in the beta-oxidation chain shortening of long-chain and very-long-chain fatty acyl-CoAs, long-chain dicarboxylyl-CoAs, the CoA esters of eicosanoids, 2-methyl-branched fatty acyl-CoAs, and the CoA esters of the bile acid intermediates, and in the process, they generate H(2)O(2). There are two complete sets of beta-oxidation enzymes present in peroxisomes, with each set consisting of three distinct enzymes. The classic PPAR alpha-regulated and inducible set participates in the beta-oxidation of straight-chain fatty acids, whereas the second noninducible set acts on branched-chain fatty acids. Long-chain and very-long-chain fatty acids are also metabolized by the cytochrome P-450 CYP4A omega-oxidation system to dicarboxylic acids that serve as substrates for peroxisomal beta-oxidation. Evidence derived from mouse models of PPAR alpha and peroxisomal beta-oxidation deficiency highlights the critical importance of the defects in PPAR alpha-inducible beta-oxidation in energy metabolism and in the development of steatohepatitis.
Reddy
J K
JK
Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611-3008, USA. jkreddy@northwestern.edu
D000818:Animals; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D005234:Fatty Liver / Q000150:complications*; D006505:Hepatitis / Q000150:complications*; D006706:Homeostasis; D006801:Humans; D010084:Oxidation-Reduction; D018901:Peroxisomal Disorders / Q000235:genetics; D020675:Peroxisomes / Q000201:enzymology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*
D005227:Fatty Acids; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors