TAILIEUCHUNG - Báo cáo khoa học: a-Methylacyl-CoA racemase – an ‘obscure’ metabolic enzyme takes centre stage

Branched-chain lipids are important components of the human diet and are used as drug molecules, . ibuprofen. Owing to the presence of methyl groups on their carbon chains, they cannot be metabolized in mitochon-dria, and instead are processed and degraded in peroxisomes. Several dif-ferent oxidative degradation pathways for these lipids are known, including a-oxidation, b-oxidation, and x-oxidation. | IFEBS Journal REVIEW ARTICLE a-Methylacyl-CoA racemase - an obscure metabolic enzyme takes centre stage Matthew D. Lloyd1 Daniel J. Darley1 Anthony S. Wierzbicki2 and Michael D. Threadgill1 1 Department of Pharmacy Pharmacology MedicinalChemistry University of Bath UK 2 Department of ChemicalPathology St Thomas Hospital London UK Keywords a-oxidation b-oxidation branched-chain fatty acid oxidation ibuprofen ro-oxidation P504S peroxisomes phytanic acid prostate cancer a-methylacyl-CoA racemase AMACR Correspondence M. D. Lloyd MedicinalChemistry Department of Pharmacy Pharmacology University of Bath Claverton Down Bath BA2 7AY UK Fax 44 1225 386114 Tel 44 1225 386786 E-mail Website http pharmacy staff Received 6 November 2007 revised 19 December 2007 accepted 14 January 2008 Branched-chain lipids are important components of the human diet and are used as drug molecules . ibuprofen. Owing to the presence of methyl groups on their carbon chains they cannot be metabolized in mitochondria and instead are processed and degraded in peroxisomes. Several different oxidative degradation pathways for these lipids are known including a-oxidation b-oxidation and x-oxidation. Dietary branched-chain lipids especially phytanic acid have attracted much attention in recent years due to their link with prostate breast colon and other cancers as well as their role in neurological disease. A central role in all the metabolic pathways is played by a-methylacyl-CoA racemase AMACR which regulates metabolism of these lipids and drugs. AMACR catalyses the chiral inversion of a diverse number of 2-methyl acids as their CoA esters and regulates the entry of branched-chain lipids into the peroxisomal and mitochondrial b-oxidation pathways. This review brings together advances in the different disciplines and considers new research in both the metabolism of branched-chain lipids and their role in cancer with particular emphasis on the crucial .

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