{{Short description|Metabolic pathway}} Enzymatic steps of alpha oxidation|right|thumb|250px '''Alpha oxidation''' ('''α-oxidation''') is a process by which certain fatty acids are broken down by removal of a single carbon from the carboxyl end. This is generally applied to fatty acids resistant to beta-oxidation, the other process for fatty acid breakdown. 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. * In the endoplasmic reticulum to break down phytosphingosine, which cannot undergo beta-oxidation due to its 4-hydroxy group, into pentadecanoic acid, which can then be beta-oxidized after acquiring CoA.

==Pathway==

=== Phytanic acid === 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 (''PHYH''), in a process using Fe<sup>2+</sup> and O<sub>2</sub>, to yield 2-hydroxyphytanoyl-CoA. #2-hydroxyphytanoyl-CoA is cleaved by 2-hydroxyphytanoyl-CoA lyase (specifically ''HACL1'') in a TPP-dependent reaction to form pristanal and formyl-CoA (in turn later broken down into formate and eventually CO<sub>2</sub>). #Pristanal is oxidized by aldehyde dehydrogenase (specifically ''ALDH3A2'') to form pristanic acid.

(Propionyl-CoA is released as a result of beta oxidation when the beta carbon is substituted)

=== Phytosphingosine === Alpha-oxidation of phytosphingosine and other sphingolipid components can entirely happen in the endoplasmic reticulum (ER), as all components of the main pathway are found in the ER.<ref name="Kitamura17">{{cite journal |last1=Kitamura |first1=T |last2=Seki |first2=N |last3=Kihara |first3=A |title=Phytosphingosine degradation pathway includes fatty acid α-oxidation reactions in the endoplasmic reticulum. |journal=Proceedings of the National Academy of Sciences of the United States of America |date=28 March 2017 |volume=114 |issue=13 |pages=E2616-E2623 |doi=10.1073/pnas.1700138114 |pmid=28289220}}</ref>

# Phytosphingosine (PHS) is phosphorylated to PHS 1-phosphate by SPH kinase. This is mainly catalyzed by ''SPHK2''. # PHS-1P is converted to 2-hydroxypalmital (2-OH C16:0-CHO) by ''SGPL1''. # 2-OH C16:0-CHO is converted to 2-hydroxypalmitate (2-OH C16:0-COOH) by ''ALDH3A2''. # 2-OH C16:0-COOH is converted to 2-hydroxypalmityl-CoA (2-OH C16:0-CoA) by one of the long-chain acyl-CoA synthetases (ACSs). # 2-OH C16:0-CoA is converted to pentadecanoal (C15:0-CHO) by ''HACL2'' (with ''HACL1'' being able to compensate if knocked out). # C15:0-CHO is converted to pentadecanoic acid (C15:0-COOH) by ''ALDH3A2''. # C15:0-COOH is converted to pentadecanoyl-CoA by one of the long-chain ACSs.

==Deficiency== Enzymatic deficiency in phytanic acid 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.

''ALDH3A2'' deficiency is known to cause the neurocutaneous disorder Sjögren–Larsson syndrome, in which accumulated aldehydes damage skin and nerve cells: cells that have the most sphingolipid turnover.<ref name="Kitamura17"/>

==References== {{reflist}} # {{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}}

Category:Biochemistry Category:Cell biology Category:Lipid metabolism Category:Metabolic pathways Category:Fatty acids