Fatty acid oxidation

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Fatty acid oxidation

Description

Fatty acid oxidation (β-oxidation) is a multi-step process by which fatty acids are broken down to generate acetyl-CoA, NADH and FADH2 for further energy transformation in the mitochondrial matrix. Whereas NADH is the substrate of CI, FADH2 is the substrate of Electron-transferring flavoprotein complex (CETF) which is localized on the matrix face of the mtIM, and supplies electrons from FADH2 to CoQ2. Before the mitochondrial transport for ß-oxidation, fatty acids (short-chain with 1-6, medium-chain with 7–12, long-chain with >12 carbon atoms) are activated by fatty acyl-CoA synthases (thiokinases) in the cytosol. For the mitochondrial transport of long-chain fatty acids the mtOM-enzyme carnitine palmitoyltransferase I (CPT-1; rate-limiting step in FAO) is required which generates an acyl-carnitine intermediate from acyl-CoA and carnitine. In the next step, an integral mtIM protein carnitine-acylcarnitine translocase (CACT) catalyzes the entrance of acyl-carnitines into the mitochondrial matrix in exchange for free carnitines. In the inner side of the mtIM, another enzyme carnitine palmitoyltransferase 2 (CPT-2) converts the acyl-carnitines to carnitine and acyl-CoAs, which undergo ß-oxidation in the mitochondrial matrix. Short- and medium-chain fatty acids do not require the carnitine shuttle for mitochondrial transport. Octanoate, but not palmitate, (eight- and 16-carbon saturated fatty acids) may pass the mt-membranes, but both are frequently supplied to mt-preparations in the activated form of octanoylcarnitine or palmitoylcarnitine.

Abbreviation: FAO

Reference: Gnaiger 2019 MitoPathways,


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Talk:Fatty acid oxidation

FAO and HRR

FAO cannot proceed without a substrate combination of fatty acids & malate, and inhibition of CI blocks FAO completely. Fatty acids are split stepwise into two carbon fragments forming acetyl-CoA, which enters the TCA cycle by condensation with oxaloacetate (CS reaction). Therefore, FAO implies simultaneous electron transfer into the Q-junction through CETF and CI.
Studies with FAO in mt-preparations are conducted with mitochondrial respiration media (MiR05Cr, MiR06, etc.) with fatty acid-free Bovine serum albumine [1], [2], [3].
The use of fatty-acid free BSA is very important when providing fatty acids in vitro, to buffer the free FA concentration and thus avoid FFA toxicity [4].
Gnaiger E, 2015-05-15


SUITbrowser question: Fatty acid oxidation

SUIT protocols can assess the respiration stimulated by fatty acid oxidation, with the participation of the electron-transferring flavoprotein complex.
The SUITbrowser can be used to find the best SUIT protocols to answer this and other research questions.

References

  1. Lemieux H, Semsroth S, Antretter H, Höfer D, Gnaiger E (2011) Mitochondrial respiratory control and early defects of oxidative phosphorylation in the failing human heart. Int J Biochem Cell Biol 43:1729–38. »Bioblast Access«
  2. Pesta D, Hoppel F, Macek C, Messner H, Faulhaber M, Kobel C, Parson W, Burtscher M, Schocke M, Gnaiger E (2011) Similar qualitative and quantitative changes of mitochondrial respiration following strength and endurance training in normoxia and hypoxia in sedentary humans. Am J Physiol Regul Integr Comp Physiol 301:R1078–87. »Open Access«
  3. Pesta D, Gnaiger E (2012) High-resolution respirometry. OXPHOS protocols for human cells and permeabilized fibres from small biopsies of human muscle. Methods Mol Biol 810:25-58. »Bioblast Access«
  4. Oliveira AF, Cunha DA, Ladriere L, Igoillo-Esteve M, Bugliani M, Marchetti P, Cnop M (2015) In vitro use of free fatty acids bound to albumin: A comparison of protocols. Biotechniques 58:228-33. »Open Access«
» O2k-Network discussion forum: fatty acids used in permeabilized fibre assays
» F-pathway control state


MitoPedia methods: Respirometry 


MitoPedia topics: Substrate and metabolite