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WIREs Syst Biol Med
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Fatty acid oxidation: systems analysis and applications

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Fatty acids (FAs) are essential components of cellular structure and energy‐generating routes in living organisms. They exist in a variety of chemical configurations and functionalities and are catabolized by different oxidative routes, according to their structure. α‐ and ω‐Oxidation are minor routes that occur only in eukaryotes, while β‐oxidation is the major degradation route in eukaroytes and prokaryotes. These pathways have been characterized and engineered from different perspectives for industrial and biomedical applications. The severity of FA oxidation disorders in humans initially guided the study of FA metabolism at a molecular‐level. On the other hand, recent advances in metabolic engineering and systems biology have powered the study of FA biosynthetic and catabolic routes in microorganisms at a systems‐level. Several studies have proposed these pathways as platforms for the production of fuels and chemicals from biorenewable sources. The lower complexity of microbial systems has allowed a more comprehensive study of FA metabolism and has opened opportunities for a wider range of applications. Still, there is a need for techniques that facilitate the translation of high‐throughput data from microorganisms to more complex eukaryotic systems in order to aid the development of diagnostic and treatment strategies for FA oxidation disorders. In addition, further systems biology analyses on human systems could also provide valuable insights on oxidation disorders. This article presents a comparison of the three main FA oxidative routes, systems biology analyses that have been used to study FA metabolism, and engineering efforts performed on microbial systems. WIREs Syst Biol Med 2013, 5:575–585. doi: 10.1002/wsbm.1226 This article is categorized under: Biological Mechanisms > Metabolism Physiology > Physiology of Model Organisms

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FA oxidation routes. (a) β‐Oxidation is the main oxidation route for most FAs. It occurs in prokaryotic cells, and in the mitochondria and peroxisomes of eukaryotes. Fatty acid transport across the mitochondrial inner membrane is facilitated by carnitine transferases and translocases (a, insert). (b) α‐Oxidation occurs in the peroxisomes of eukaryotes and is the main route for 3‐methyl branched‐ and straight long‐chain FAs in preparation for β‐oxidation, in which they are fully oxidized. (c) ω‐Oxidation is a minor pathway that occurs in eukaryotes for the degradation of long‐ and very long‐chain FAs into dicarboxylate. Abbreviations: 2‐OG, 2‐oxoglutarate; ‐MB‐, Methyl Branched; ‐StC‐, Straight Chain; CPT I, Carnitine Palmitoyl Transferase I; CACT, Carntine‐Acylcarnitine Translocase; CPT II, Carnitine Palmitoyl Transferase II.
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