Alpha oxidation


[image:Alpha oxidation.svg|Enzymatic steps of alpha oxidation|right|thumb|250px]
Alpha oxidation is a process by which certain branched-chain 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 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.
  4. Pristanal is oxidized by aldehyde dehydrogenase to form pristanic acid.

Deficiency

Enzymatic deficiency in alpha-oxidation 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.