Phytanoyl-CoA 2-hydroxylase (PHYH)

Phytanoyl-CoA 2-hydroxylase (PHYH, also called PAHX) is a peroxisomal, Fe(II) and 2-oxoglutarate-dependent oxygenase that catalyzes the first step of alpha-oxidation in the degradation of phytanic acid, a branched-chain fatty acid derived from chlorophyll metabolism in humans[1][2][3][4][5]. PHYH is essential because phytanic acid cannot be metabolized by the more common beta-oxidation pathway due to its methyl group structure; instead, PHYH hydroxylates phytanoyl-CoA to initiate alpha-oxidation, allowing breakdown to continue[1][2]. Deficiency or mutations in PHYH cause accumulation of phytanic acid, leading to Refsum disease, a rare neurodegenerative disorder characterized by retinitis pigmentosa, peripheral neuropathy, cerebellar ataxia, and other systemic symptoms[2][3][5][10]. The gene encoding PHYH is located on chromosome 10p13 and is highly conserved in mammals. No direct small molecule drugs currently target PHYH; therapeutic approaches focus on dietary restriction of phytanic acid to prevent its accumulation in affected individuals[10].

Other names

Phytanoyl-CoA dioxygenaseperoxisomal phytanoyl-CoA 2-hydroxylasePAHXPhyHPhytanic acid oxidasePhytanoyl-CoA alpha-hydroxylaseRefsum disease proteinphytanoyl-CoA alpha hydroxylasephytanoyl-CoA 2-oxoglutarate dioxygenase

Enzyme replacement or function restoration (conceptual/experimental only); dietary management to reduce phytanic acid accumulation (substrate reduction)[10]