tailieunhanh - Báo cáo khoa học: Fatty acid omega-oxidation as a rescue pathway for fatty acid oxidation disorders in humans

Fatty acids (FAs) can be degraded via different mechanisms including a-, b- and x-oxidation. In humans, a range of different genetic diseases has been identified in which either mitochondrial FAb-oxidation, peroxisomal FAb-oxidation or FAa-oxidation is impaired. Treatment options for most of these disorders are limited. | IFEBS Journal MINIREVIEW Fatty acid omega-oxidation as a rescue pathway for fatty acid oxidation disorders in humans Ronald J. A. Wanders Jasper Komen and Stephan Kemp Academic MedicalCenter University of Amsterdam The Netherlands Keywords adrenoleukodystrophy cytochrome P450 fatty acids mitochondria peroxisomes Refsum disease Zellweger syndrome a-oxidation b-oxidation ffi-oxidation Correspondence R. J. A. Wanders Genetic Metabolic Diseases Room F0-226 Academic Medical Center University of Amsterdam Meibergdreef 9 1105 AZ Amsterdam The Netherlands Fax 31 0 20 6962596 Tel 31 0 20 5665958 5664197 E-mail Received 22 June 2010 revised 28 September 2010 accepted 3 November 2010 doi Fatty acids FAs can be degraded via different mechanisms including a- b- and ro-oxidation. In humans a range of different genetic diseases has been identified in which either mitochondrial FA b-oxidation peroxisomal FA b-oxidation or FA a-oxidation is impaired. Treatment options for most of these disorders are limited. This has prompted us to study FA x-oxida-tion as a rescue pathway for these disorders based on the notion that if the x-oxidation of specific FAs could be upregulated one could reduce the accumulation of these FAs and the subsequent detrimental effects in the different groups of disorders. In this minireview we describe our current state of knowledge in this area with special emphasis on Refsum disease and X-linked adrenoleukodystrophy. Introduction In general fatty acids FAs can be degraded via different mechanisms including a- b- and x-oxidation Fig. 1 . In humans a-oxidation takes place in peroxisomes only whereas both peroxisomes and mitochondria are able to b-oxidize FAs. Importantly in recent years a great number of genetically determined disorders in humans has been described in which either FA a-oxidation or FA b-oxidation in mitochondria or peroxisomes is deficient. As discussed in more detail below treatment .