Peroxisomal α-oxidation

Branched-chain phytanic acid, a product of chlorophyll metabolism, is not a substrate for acyl CoA dehydrogenase because of the methyl group on its β-carbon (Fig. 1). Instead, it is hydroxylated at the α-carbon by phytanoyl CoA α-hydroxylase (PhyH); carbon 1 is released as CO2; and the product, 15-carbon-long pristanal, is oxidized to pristanic acid, which is activated to its CoA derivative and undergoes β-oxidation. Refsum disease is a rare, autosomal-recessive disorder caused by a deficiency of peroxisomal PhyH.

This results in the accumulation of phytanic acid in the plasma and tissues. The symptoms are primarily neurologic, and the treatment involves dietary restriction to halt disease progression. [Note: ω-Oxidation (at the methyl terminus) also is known and generates dicarboxylic acids. Normally a minor pathway of the SER, its upregulation is seen with conditions such as MCAD deficiency that limit fatty acid β-oxidation.]

Figure 1: Phytanic acid, a branched-chain fatty acid 16 carbons in length.