phytanoylCoA

Phytanoyl-CoA is the coenzyme A thioester of phytanic acid, a branched-chain fatty acid found in animal fats. It is formed when phytanic acid is activated by CoA through the action of acyl-CoA synthetases, a prerequisite for its subsequent metabolism in peroxisomes. As a metabolic intermediate, phytanoyl-CoA participates in the peroxisomal alpha-oxidation pathway that handles branched fatty acids that are not readily processed by standard beta-oxidation.

In peroxisomal alpha-oxidation, phytanoyl-CoA is hydroxylated at the alpha carbon by phytanoyl-CoA hydroxylase (PHYH), a 2-oxoglutarate-dependent dioxygenase that requires oxygen. This reaction produces 2-hydroxyphytanoyl-CoA. The ensuing step, catalyzed by 2-hydroxyphytanoyl-CoA lyase (HACL1), cleaves the molecule to pristanal and formyl-CoA. Pristanal is subsequently oxidized to pristanic acid, which is then activated to pristanoyl-CoA and enters beta-oxidation, again largely within peroxisomes, for energy production.

Clinical significance commonly arises from defects in PHYH or in peroxisome biogenesis, leading to accumulation of phytanic acid in tissues and plasma. This condition, associated with Refsum disease, presents with retinitis pigmentosa, peripheral neuropathy, ataxia, and skin changes. Management typically includes dietary restriction of phytanic acid-containing foods and monitoring of peroxisomal function. Phytanoyl-CoA measurements and phytanic acid levels are used in diagnostic evaluations of peroxisomal disorders and related metabolic diseases.