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P EROXISOMAL β-O XIDATION AND P EROXISOME P ROLIFERATOR–A CTIVATED R ECEPTOR α: An Adaptive Metabolic System
Abstract
▪ Abstract β-Oxidation occurs in both mitochondria and peroxisomes. Mitochondria catalyze the β-oxidation of the bulk of short-, medium-, and long-chain fatty acids derived from diet, and this pathway constitutes the major process by which fatty acids are oxidized to generate energy. Peroxisomes are involved in the β-oxidation chain shortening of long-chain and very-long-chain fatty acyl-coenzyme (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 di- and trihydroxycoprostanoic acids, and in the process they generate H 2 O 2. Long-chain and very-long-chain fatty acids (VLCFAs) are also metabolized by the cytochrome P450 CYP4A ω-oxidation system to dicarboxylic acids that serve as substrates for peroxisomal β-oxidation. The peroxisomal β-oxidation system consists of (a) a classical peroxisome proliferator–inducible pathway capable of catalyzing straight-chain acyl-CoAs by fatty acyl-CoA oxidase, L-bifunctional protein, and thiolase, and (b) a second noninducible pathway catalyzing the oxidation of 2-methyl-branched fatty acyl-CoAs by branched-chain acyl-CoA oxidase (pristanoyl-CoA oxidase/trihydroxycoprostanoyl-CoA oxidase), D-bifunctional protein, and sterol carrier protein (SCP)x. The genes encoding the classical β-oxidation pathway in liver are transcriptionally regulated by peroxisome proliferator–activated receptor α (PPARα). Evidence derived from mice deficient in PPARα, peroxisomal fatty acyl-CoA oxidase, and some of the other enzymes of the two peroxisomal β-oxidation pathways points to the critical importance of PPARα and of the classical peroxisomal fatty acyl-CoA oxidase in energy metabolism, and in the development of hepatic steatosis, steatohepatitis, and liver cancer.
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Metadata
- Authors
- Reddy, J. K., & Hashimoto, T.
- Venue
- Annual Review of Nutrition
- Publisher
- Annual Reviews
- Published
- 2001-07
- Volume
- 21
- Issue
- 1
- Pages
- 193-230
- ISSN
- 0199-9885 (ISSN-L)
- 1545-4312
- OpenAlex
- W2104492370
- Cited by
- 959
- References
- 12
- FWCI
- 1.48
- Type
- journal article
- Language
- en
- Open access
- closed
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