Alpha oxidation explained

Enzymatic steps of alpha oxidation|right|thumb|250pxAlpha 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.

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)

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.

Notes and References

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 . en . 278 . 2 . 182–194 . 10.1111/j.1742-4658.2010.07947.x. 21156023 . 32017693 . free .