Difference between revisions of "Fatty acid oxidation"

Latest revision as of 09:27, 8 May 2023

high-resolution terminology - matching measurements at high-resolution

Fatty acid oxidation

Description

Fatty acid oxidation is a multi-step process by which fatty acids are broken down in β-oxidation to generate acetyl-CoA, NADH and FADH₂ for further electron transfer to CoQ. 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 CoQ. Before the ß-oxidation in the mitochondrial matrix, 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; considered as a 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 2020 BEC MitoPathways

MitoPedia O2k and high-resolution respirometry: O2k-Open Support

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

↑ 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«
↑ 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«
↑ 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«
↑ 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

Labels:

MitoPedia:FAT4BRAIN

[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«

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[2]

[3]

[4]

@@ Line 1: / Line 1: @@
 {{MitoPedia
 |abbr=FAO
-|description=Fatty acids (short chain with 4–8, medium-chain with 6–12, long chain with 16-22 carbon atoms) are activated by fatty acyl-CoA synthases (thiokinases) in the cytosol. The outer mt-membrane enzyme carnitine palmitoyltransferase 1 (CPT-1) generates an acyl-carnitine intermediate for transport into the mt-matrix. [[Octanoate]] and [[palmitate]] (eight- and 16-carbon saturated fatty acids) may pass the mt-membranes but are frequently supplied to mt-preparations in the activated form of [[octanoylcarnitine]] or [[palmitoylcarnitine]].
+|description='''Fatty acid oxidation''' is a multi-step process by which [[fatty acid]]s are broken down in [[β-oxidation]] to generate acetyl-CoA, NADH and FADH<sub>2</sub> for further electron transfer to CoQ. Whereas NADH is the substrate of CI, FADH<sub>2</sub> is the substrate of [[electron-transferring flavoprotein complex]] (CETF) which is localized on the matrix face of the mtIM, and supplies electrons from FADH<sub>2</sub> to CoQ. Before the ß-oxidation in the mitochondrial matrix, 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; considered as a 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]].
+|info=[[Gnaiger 2020 BEC MitoPathways]]
+}}
+__TOC__
+{{Technical support integrated}}
+ [[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]] <ref> 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. [[Lemieux 2011 Int J Biochem Cell Biol |»Bioblast Access«]] </ref>, <ref> 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. [[Pesta 2011 Am J Physiol Regul Integr Comp Physiol |»Open Access«]] </ref>, <ref> 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. [[Pesta 2012 Methods Mol Biol |»Bioblast Access«]] </ref>.
+:::: 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  <ref> 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. [[Oliveira 2015 Biotechniques |»Open Access«]] </ref>.
+:::: [[Gnaiger E]], 2015-05-15
-[[Electron-transferring flavoprotein complex]] (CETF) is located on the matrix face of the inner mt-membrane, and supplies electrons from fatty acid β-oxidation (FAO) to CoQ. 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]] trough CETF and CI.
-|info=Gnaiger 2014 MitoPathways
+== [[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 [https://suitbrowser.oroboros.at/ SUITbrowser] can be used to find the best SUIT protocols to answer this and other research questions.
+== References ==
+<references/>
+:» [[Talk:Fatty acid oxidation |O2k-Network discussion forum: fatty acids used in permeabilized fibre assays]]
+:» [[F-pathway control state]]
 {{MitoPedia methods
 |mitopedia method=Respirometry
@@ Line 12: / Line 31: @@
 {{MitoPedia topics
 |mitopedia topic=Substrate and metabolite
+}}
+{{Labeling
+|additional=MitoPedia:FAT4BRAIN
 }}