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Am J Physiol Gastrointest Liver Physiol 281: G1333-G1339, 2001;
0193-1857/01 $5.00
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Vol. 281, Issue 6, G1333-G1339, December 2001

THEME
Nonalcoholic Steatosis and Steatohepatitis
III. Peroxisomal beta -oxidation, PPARalpha , and steatohepatitis

Janardan K. Reddy

Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611-3008

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 H2O2. There are two complete sets of beta -oxidation enzymes present in peroxisomes, with each set consisting of three distinct enzymes. The classic PPARalpha -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 PPARalpha and peroxisomal beta -oxidation deficiency highlights the critical importance of the defects in PPARalpha -inducible beta -oxidation in energy metabolism and in the development of steatohepatitis.

peroxisomes; fatty acid beta - and omega -oxidation; peroxisomal proliferator-activated receptor alpha ; peroxisomal biogenesis disorders


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