View source for Beta oxidation

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==Overview==
'''Beta oxidation''' is the process by which [[fatty acid]]s, in the form of [[Acyl-CoA]] molecules, are broken down in the [[mitochondria]] and/or in [[peroxisome]]s to generate [[Acetyl-CoA]], the entry molecule for the [[Krebs Cycle]]. 

Occurs in mitochondrial matrix.
[[Image:LCHAD deficiency.jpg|center|thumb|370px|Schematic demonstrating [[mitochondria]]l [[fatty acid]] [[beta-oxidation]] and effects of LCHAD deficiency]]

==Four recurring steps==
Once inside the mitochondria, the β-oxidation of fatty acids occurs via four recurring steps:

{| class="wikitable"
| '''Description''' || '''Diagram''' || '''Enzyme''' || '''End product'''
 |- 
 | ''[[Oxidation]] by [[flavin|FAD]]:'' The first step is the oxidation of the fatty acid by Acyl-CoA-Dehydrogenase. The enzyme catalyzes the formation of a [[double bond]] between the C-2 and C-3.  || [[Image:Beta-Oxidation1.svg|center|400px]] || [[acyl CoA dehydrogenase]] || trans-Δ<sup>2</sup>-enoyl-CoA
 |- 
 | ''[[Hydration]]:'' The next step is the [[hydration reaction|hydration]] of the bond between C-2 and C-3. The reaction is [[stereospecific]], forming only the L [[isomer]]. || [[Image:Beta-Oxidation2.svg|center|400px]] ||  [[enoyl CoA hydratase]]  || L-3-hydroxyacyl CoA
 |- 
 | ''[[Oxidation]] by [[NADH|NAD<sup>+</sup>]]:'' The third step is the [[oxidation]] of L-3-hydroxyacyl CoA by NAD<sup>+</sup>. This converts the [[hydroxyl]] group into a [[keto]] group. || [[Image:Beta-Oxidation3.svg|center|400px]] || [[L-3-hydroxyacyl CoA dehydrogenase]]  || 3-ketoacyl CoA
 |- 
 | ''[[Thiolysis]]:'' The final step is the cleavage of 3-ketoacyl CoA by the [[thiol]] group of another molecule of [[CoA]]. The thiol is inserted between C-2 and C-3. || [[Image:Beta-Oxidation4.svg|center|400px]] || [[Β-ketothiolase]]  || An [[acetyl CoA]] molecule, and an [[acyl CoA]] molecule, which is two carbons shorter 
|}

This process continues until the entire chain is cleaved into acetyl CoA units. For every cycle, the Acyl CoA unit is shortened by two carbon atoms. Concomitantly, one molecule of FADH<sub>2</sub>, NADH and acetyl CoA are formed.

==β-oxidation of unsaturated fatty acids==
β-oxidation of unsaturated fatty acids poses a problem since the location of a cis bond can prevent the formation of a trans-δ<sup>2</sup> bond. These situations are handled by an additional two enzymes.

Whatever the conformation of the hydrocarbon chain, β-oxidation occurs normally until the acyl CoA (because of the presence of a double bond) is not an appropriate substrate for ''acyl CoA dehydrogenase'', or ''enoyl CoA hydratase'':

* If the acyl CoA contains a ''cis-Δ<sup>3</sup> bond'', then ''cis-δ<sup>3</sup>-[[Enoyl CoA isomerase]]'' will convert the bond to a trans-Δ<sup>2</sup> bond, which is a regular substrate.

* If the acyl CoA contains a ''cis-Δ<sup>4</sup> double bond'', then its dehydrogenation yields a 2,4-dienoyl intermediate, which is not a substrate for enoyl CoA hydratase. However, the enzyme ''[[2,4 Dienoyl CoA reductase]]'' reduces the intermediate, using NADPH, into trans-Δ<sup>3</sup>-enoyl CoA. As in the above case, this compound is converted into a suitable intermediate by cis-Δ<sup>3</sup>-Enoyl CoA isomerase.

To summarize:
* ''odd numbered'' double bonds are handled by the isomerase.
* ''even numbered'' bonds by the reductase (which creates an odd numbered double bond) and the isomerase.

==β-oxidation of odd-numbered chains==
Chains with an odd-number of [[carbon]]s are oxidized in the same manner as even-numbered chains, but the final products are [[propionyl CoA]] and [[acetyl CoA]]. 

Propionyl CoA is converted into [[succinyl CoA]] (which is an intermediate in the [[citric acid cycle]]) in a reaction that involves [[Vitamin B12]]. Succinyl CoA can then enter the citric acid cycle.  

Because it cannot be completely metabolized in the citric acid cycle, the products of its partial reaction must be removed in a process called [[cataplerosis]]. This allows regeneration of the citric acid cycle intermediates, possibly an important process in certain metabolic diseases.

==Oxidation in peroxisomes==
Fatty acid oxidation also occurs in [[peroxisome]]s. However, the oxidation ceases at [[octanyl CoA]]. 

One significant difference is that oxidation in peroxisomes is not coupled to [[Adenosine triphosphate|ATP]] synthesis. Instead, the high-potential electrons are transferred to O<sub>2</sub>, which yields H<sub>2</sub>O<sub>2</sub>. The enzyme [[catalase]], found exclusively in peroxisomes, converts the [[hydrogen peroxide]] into [[water]] and [[oxygen]].
It is believed that very long chain (C-22)fatty acids undergo initial oxidation in peroxisomes which is followed by mitochondrial oxidation.
Peroxisomal oxidation is induced by high fat diet and administration of hypolipidemic drugs like clofibrate.

==Energy yield==
The ATP yield for every oxidation cycle is 14 ATP, broken down as follows:

{| class="wikitable"
| '''Source''' || '''ATP''' || '''Total'''
 |- 
 |  1 [[FADH2|FADH<sub>2</sub>]] || x 1.5 ATP  || = 1.5 ATP (some sources say 2 ATP)
 |- 
 |  1 [[NADH]] || x 2.5 ATP  || = 2.5 ATP (some sources say 3 ATP)
 |- 
 | 1 [[acetyl CoA]] ||  x 10 ATP  || = 10 ATP (some sources say 12 ATP)
 |- 
 | TOTAL  ||     || = 14 ATP
|}

For an even-numbered saturated fat (C<sub>2n</sub>), n - 1 oxidations are necessary and the final process yields an additional acetyl CoA. In addition, two equivalents of [[Adenosine triphosphate|ATP]] are lost during the activation of the fatty acid. Therefore, the total ATP yield can be stated as: 

:(n - 1) * 14 + 10 - 2 = total ATP

For instance, the ATP yield of [[palmitate]] (C<sub>16</sub>, ''n = 8'') is:

:(8 - 1) * 14 + 10 - 2 = 106 ATP

Represented in table form:

{| class="wikitable"
| '''Source''' || '''ATP''' || '''Total'''
 |- 
 |  7 FADH<sub>2</sub> || x 1.5 ATP  || = 10.5 ATP
 |- 
 |  7 NADH || x 2.5 ATP  || = 17.5 ATP
 |- 
 | 8 acetyl CoA ||  x 10 ATP  || = 80 ATP
 |- 
 | Activation ||     || = -2 ATP
 |- 
 | TOTAL  ||     || = 106 ATP
|}

For sources that use the larger ATP production numbers described above, the total would be 129 ATP equivalents per palmitate.

==See also ==

*[[Fatty acid metabolism]]
*[[Krebs cycle]]
*[[Omega oxidation]]

== External links ==
*[http://www.ufp.pt/~pedros/bq/fatty.htm The chemical logic behind fatty acid metabolism] at ufp.pt
*[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db=books&doptcmdl=GenBookHL&term=oxidation+yield+AND+stryer%5Bbook%5D+AND+216592%5Buid%5D&rid=stryer.section.3050#3060  JEREMY M. BERG,JOHN L. TYMOCZKO and LUBERT STRYER Biochemistry, 2002 ]
* [http://www.brookscole.com/chemistry_d/templates/student_resources/shared_resources/animations/carnitine/carnitine1.html Animations] at brookscole.com

{{Lipid metabolism}}
{{Lipid metabolism enzymes}}


[[Category:Cell biology]]
[[Category:Metabolic pathways]]
[[Category:Fatty acids]]
[[Category:Citric acid cycle]]
[[Category:Cellular respiration]]

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[[es:Beta oxidación]]
[[fr:Bêta-oxydation]]
[[it:Beta ossidazione]]
[[ja:β酸化]]
[[lb:Beta Oxydatioun]]
[[pl:Beta-oksydacja]]
[[sv:Beta-oxidation]]
[[zh:Β-氧化]]

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