Alpha oxidation

Enzymatic steps of alpha oxidation

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 Fe²⁺ 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. , Patti A.; Eaton Simon, eds. (1999), Current views of fatty acid oxidation and ketogenesis : from organelles to point mutations, 466 (2nd ed.), New York, NY: Kluwer Acad./Plenum Publ., pp. 292–295, ISBN 0-306-46200-1