Alphaoxidation

Alpha-oxidation is a biochemical pathway that enables the catabolism of certain branched-chain fatty acids whose beta-oxidation is hindered by methyl branches at the beta position. The best-known substrate is phytanic acid, a C20 fatty acid with a methyl group at the beta carbon, which blocks conventional beta-oxidation.

In animal cells, alpha-oxidation takes place mainly in peroxisomes. The initial step is catalyzed by phytanoyl-CoA 2-hydroxylase (encoded by PHYH), which introduces a hydroxyl group at the alpha carbon of phytanoyl-CoA to form 2-hydroxyphytanoyl-CoA. This intermediate is then oxidatively cleaved by a lyase to yield pristanoyl-CoA and formyl-CoA. The pristanoyl-CoA can then enter the normal beta-oxidation pathway after shortening by successive cycles, eventually producing acetyl-CoA units for energy.

Physiological and clinical relevance: Alpha-oxidation allows branched-chain fatty acids to be degraded despite beta-oxidation blockage. Deficiency of PHYH or related peroxisomal enzymes causes Refsum disease, characterized by elevated phytanic acid levels and symptoms such as retinitis pigmentosa, peripheral neuropathy, ataxia, and skin changes. Diagnosis often involves measurement of serum phytanic acid; management includes dietary restriction of phytanic acid and sometimes plasmapheresis.

Additional notes: Alpha-oxidation is relatively slow and peroxisomal; it represents a complementary pathway to beta-oxidation for specific fatty acids and contributes to energy metabolism and detoxification of certain dietary or microbial metabolites.