- Alpha – oxidation is defined as the oxidation of fatty acid (methyl group at beta carbon) with the removal of one carbon unit adjacent to the α-carbon from the carboxylic end.
- The carbon unit is removed in the form of CO2.
- Alpha oxidation occurs in those fatty acids that have a methyl group (-CH3) at the beta-carbon, which blocks beta oxidation.
- There is no production of ATP.
Peroxisomes are the cellular sites for α-oxidation.
- Substrate: Phytanic acid, which is present in milk or derived from phytol present in chlorophyll and animal fat.
- Phytanic acid is a 20-carbon, branched-chain fatty acid.
- Branched chain fatty acids are oxidized at the α-carbon (mainly in brain and other nervous tissue), and the carboxyl carbon is released as CO2. Branches can interfere with the normal β-oxidation pathway, most often at the acyl-CoA dehydrogenase step.
- The fatty acid is thus degraded by one carbon initially, and then two carbons at a time. Both acetyl-CoA and propionyl-CoA are products if the branches are methyl groups.
Steps of alpha oxidation
- Activation of phytanic acid
- Removal of formyl CoA (CO2)
- Oxidation of Pristanal
- Beta-oxidation of pristanic acid
- Phytanic acid is first attached to CoA to form phytanoyl-CoA.
- Phytanoyl-CoA is oxidized by phytanoyl-CoA dioxygenase, in a process using Fe2+and O2, to yield 2-hydroxyphytanoyl-CoA.
- 2-hydroxyphytanoyl-CoA is cleaved by 2-hydroxyphytanoyl-CoA lyase in a TPP-dependent reaction to form pristanal and formyl-CoA (in turn later broken down into formate and eventually CO2).
- Pristanal is oxidized by aldehyde dehydrogenase to form pristanic acid (which can then undergo beta-oxidation).
- Propionyl-CoA is released as a result of beta oxidation when the beta carbon is substituted.
Significance of alpha oxidation
- α- oxidation is important in the catabolism of branched-chain fatty acids.
- Oxidation of methylated fatty acid.
- Production of cerebronic acid which synthesizes cerebroside and sulfatides.
- Production of odd chain fatty acids.
- The reaction is also a route for the synthesis of hydroxy fatty acids. The α-hydroxy fatty acid can be further oxidized and decarboxylated to a fatty acid one carbon shorter than the original. Thus, if an odd-chain-length compound is used initially, an even-chain-length acid is produced that can be further oxidized by β-oxidation.
- Refsum’s disease is the only defect in peroxisomal α-oxidation currently known.
- The Refsum’s disease is an autosomal recessive disorder and is the deficiency of phytanoyl-CoA hydroxylase.
- The clinical characteristics of Refsum’s disease include peripheral neuropathy and ataxia, retinitis pigmentosa, and abnormalities of skin and bones.
- Smith, C. M., Marks, A. D., Lieberman, M. A., Marks, D. B., & Marks, D. B. (2005). Marks’ basic medical biochemistry: A clinical approach. Philadelphia: Lippincott Williams & Wilkins.
- Rodwell, V. W., Botham, K. M., Kennelly, P. J., Weil, P. A., & Bender, D. A. (2015). Harper’s illustrated biochemistry (30th ed.). New York, N.Y.: McGraw-Hill Education LLC.