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6 Biochemistry

6a Alpha-oxidation of phytanic acid

Phytanic acid (3,7,11,15-tetramethylhexadecanoic acid) is derived from dietary sources only, mainly from dairy and ruminant fats. Phytanic acid is a 3-methyl branched chain fatty acid, which cannot undergo straightforward beta-oxidation like other fatty acids since the presence of the methyl group at the 3-position blocks beta-oxidation. Nature has resolved this problem by creating an alpha-oxidation mechanism in which the terminal carboxyl group is released as CO2. Accordingly, phytanic acid first undergoes alpha-oxidative chain shortening to produce pristanic acid (2,4,6,10-tetramethylpentadecanoic acid) and CO2. All steps from phytanoyl-CoA to pristanic acid occur in peroxisomes [Wanders et al 2001]:

*In case of a deficiency at the level of the PTS2 receptor, phytanoyl-CoA hydroxylase cannot be properly imported into the peroxisome leading to its functional deficiency.

**The other enzymes from the phytanic acid alpha-oxidation route, including 2-hydroxy phytanoyl-CoA lyase and very-long-chain acyl-CoA synthetase, are PTS1 proteins, which are targeted to the peroxisome by means of the PTS1 receptor, encoded by the PEX5 gene.

6b Beta-oxidation

Once pristanic acid has been activated to pristanoyl-CoA it undergoes three cycles of beta-oxidation in the peroxisomes to generate 4,8-dimethylnonanoyl-CoA, which then is transported to mitochondria for final oxidation to CO2 and H2O in the form of its carnitine ester.

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Page last updated 26 June 2006