Alpha oxidation
Alpha oxidation (α-oxidation) is a process by which certain branched-chain{{Cite journal |last1=Wanders |first1=Ronald J. A. |last2=Komen |first2=Jasper |last3=Kemp |first3=Stephan |date=9 November 2010 |title=Fatty acid omega-oxidation as a rescue pathway for fatty acid oxidation disorders in humans: Fatty acid oxidation disorders |journal=FEBS Journal |language=en |volume=278 |issue=2 |pages=182–194 |doi=10.1111/j.1742-4658.2010.07947.x|pmid=21156023 |s2cid=32017693 |doi-access=free }} 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.
References
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- {{citation|doi=10.1046/j.1432-1033.2003.03534.x|pmid=12694175|year=2003|last1=Casteels|first1=M|last2=Foulon|last3=Mannaerts|last4=Van Veldhoven|title=Alpha-oxidation of 3-methyl-substituted fatty acids and its thiamine dependence|volume=270|issue=8|pages=1619–1627|journal=European Journal of Biochemistry|first2=V|first3=GP|first4=PP|doi-access=free}}
- {{citation|isbn=0-306-46200-1|pages=292–295|editor1=Quant, Patti A.|editor2=Eaton, Simon|edition=2nd|volume=466|year=1999|publisher=Kluwer Acad./Plenum Publ.|location=New York, NY|title=Current views of fatty acid oxidation and ketogenesis : from organelles to point mutations}}
{{Lipid metabolism enzymes}}