Alpha oxidation

Enzymatic steps of alpha oxidation

Alpha oxidation (α-oxidation) is a process by which certain branched-chain[1] fatty acids are broken down by removal of a single carbon from the carboxyl end. In humans, alpha-oxidation is used in peroxisomes to break down dietary phytanic acid, which cannot undergo beta-oxidation due to its β-methyl branch, into pristanic acid. Pristanic acid can then acquire CoA and subsequently become beta oxidized, yielding propionyl-CoA.

Pathway

Alpha-oxidation of phytanic acid is believed to take place entirely within peroxisomes.

1. Phytanic acid is first attached to CoA to form phytanoyl-CoA.
2. Phytanoyl-CoA is oxidized by phytanoyl-CoA dioxygenase, in a process using Fe^2+ and O₂, to yield 2-hydroxyphytanoyl-CoA.
3. 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).
4. 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)

Deficiency

Enzymatic deficiency in alpha-oxidation (most frequently in phytanoyl-CoA dioxygenase) leads to Refsum's disease, in which the accumulation of phytanic acid and its derivatives leads to neurological damage. Other disorders of peroxisome biogenesis also prevent alpha-oxidation from occurring.

References

1. Wanders, Ronald J. A.; Komen, Jasper; Kemp, Stephan (9 November 2010). "Fatty acid omega-oxidation as a rescue pathway for fatty acid oxidation disorders in humans: Fatty acid oxidation disorders". FEBS Journal. 278 (2): 182–194. doi:10.1111/j.1742-4658.2010.07947.x. PMID 21156023. S2CID 32017693.

1. Casteels, M; Foulon, V; Mannaerts, GP; Van Veldhoven, PP (2003), "Alpha-oxidation of 3-methyl-substituted fatty acids and its thiamine dependence", European Journal of Biochemistry, 270 (8): 1619–1627, doi:10.1046/j.1432-1033.2003.03534.x, PMID 12694175
2. Quant, Patti A.; Eaton, Simon, eds. (1999), Current views of fatty acid oxidation and ketogenesis : from organelles to point mutations, vol. 466 (2nd ed.), New York, NY: Kluwer Acad./Plenum Publ., pp. 292–295, ISBN 0-306-46200-1