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Beta Oxidation of Acyl-CoA

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The second step of fatty acid degradation is beta oxidation.  Fats are broken down and converted to Acyl-CoA for beta oxidation to be used as energy sources during high energy demands such as exercise.[1]   When energy demands are high, hormone secretions release fatty acids from adipose tissues so they can be broken down for energy when alternate energy sources are low in concentration.[1]

Beta oxidation occurs in the mitochondria of the cell.[2]  After activation of fatty acids in the cytosol, Acyl-CoA must be transported to the mitochondria so that beta oxidation can break down Acyl-CoA to provide energy.  There are no transport proteins to bring Acyl-CoA into the mitochondria, so to get into the mitochondria carnitine palmitoyltransferase 1 (CPT1) converts Acyl-CoA into acylcarnitine which gets transported into the mitochondrial matrix.[1]  Once in the matrix, acylcarnitine is converted back to Acyl-CoA by CPT2.[2]  Beta oxidation may begin now that Acyl-CoA is in the mitochondria.  

There are four steps to beta oxidation once the Acyl-CoA has entered the matrix.

1.      Acyl-CoA dehydrogenase removes 2 hydrogens from Acyl-CoA to create a double bond between the alpha and beta carbons. [3]  This also reduces FAD to FADH2.[4]

2.      Enoyl-CoA hydrase adds water across the newly formed double bond to make an alcohol.[2][3]

3.      3-hydroxyacyl-CoA dehydrogenase oxidizes the alcohol group to a ketone.[2] This produces one molecule of NADH from NAD+.[3]

4.      Thiolase cleaves between the alpha carbon and ketone to release one molecule of Acetyl-CoA and the Acyl-CoA which is now 2 carbons shorter.[3]

This four step process repeats until Acyl-CoA has removed all carbons from the chain, leaving only Acetyl-CoA. During one cycle of beta oxidation, Acyl-CoA creates one molecule of Acetyl-CoA, FADH2, and NADH.[4]  Acetyl-CoA is then used in the citric acid cycle while FADH2 and NADH are sent to the electron transport chain.[5] These intermediates all end up providing energy for the body as they are ultimately converted to ATP.[5]

The process of Beta Oxidation of an activated Acyl-CoA molecule.
Example of Beta Oxidation using Stearic Acid

Beta oxidation, as well as alpha-oxidation, also occurs in the peroxisome.[1] The peroxisome handles beta oxidation of fatty acids that have more than 20 carbons in their chain because the peroxisome contains very-long-chain Acyl-CoA synthetases.[6]  These enzymes are better equipped to oxidize Acyl-CoA with long chains that the mitochondria cannot handle.

Example using Stearic Acid
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Beta oxidation removes 2 carbons at a time, so in the oxidation of an 18 carbon fatty acid such as Stearic Acid 8 cycles will need to occur to completely break down Acyl-CoA.[6] This will produce 9 Acetyl-CoA that have 2 carbons each, 8 FADH2, and 8 NADH.  

  1. ^ a b c d Talley, Jacob T.; Mohiuddin, Shamim S. (2020), "Biochemistry, Fatty Acid Oxidation", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 32310462, retrieved 2021-02-23
  2. ^ a b c d "Fatty acid beta oxidation | Abcam". www.abcam.com. Retrieved 2021-02-23.
  3. ^ a b c d "6.11: Fatty Acid Oxidation". Biology LibreTexts. 2016-02-26. Retrieved 2021-02-23.
  4. ^ a b Editors, B. D. (2017-06-03). "Beta Oxidation". Biology Dictionary. Retrieved 2021-02-23. {{cite web}}: |last= has generic name (help)
  5. ^ a b "6.32 Fatty Acid Oxidation (Beta-oxidation) | Nutrition Flexbook". courses.lumenlearning.com. Retrieved 2021-02-23.
  6. ^ a b Reddy, Janardan K; Hashimoto, Takashi (2001-07-01). "PEROXISOMAL β-OXIDATION AND PEROXISOME PROLIFERATOR–ACTIVATED RECEPTOR α: An Adaptive Metabolic System". Annual Review of Nutrition. 21 (1): 193–230. doi:10.1146/annurev.nutr.21.1.193. ISSN 0199-9885.