Evidence against α-hydroxyphytanic acid as an intermediate in the metabolism of phytanic acid

Abstract

It was established 20 years ago that phytanic acid is degraded by an initial α-oxidation, and that α-hydroxyphytanic acid is an intermediate in the reaction. Patients with Refsum's disease, as well as those with the α-called peroxisomal disorders, have an enzymatic defect in this a-oxidation. The present work shows that when cultured skin fibroblasts from both groups of patients as well as from healthy controls are incubated with (1-¹⁴C)phytanic acid, the only radioactive compounds which can be detected are ¹⁴CO₂ and unmetabolised phytanic acid. The degradation of (1-¹⁴C)α-hydroxyphytanic acid to ¹⁴CO₂ takes place in the mitochondrial fraction of rat liver. Unlabelled α-hydroxyphytanic acid added to rat liver homogenate or mitochondria and (1-¹⁴C)phytanic acid reduced considerably the production of ¹⁴CO₂. However, ¹⁴C-labelling of the α-hydroxyphytanic acid pool did not occur. Thus, we have been unable to confirm the previous demonstration of α-hydroxyphytanic acid as an intermediate in the degradation of phytanic acid.

Key Words:

• α-oxidation
• peroxisomal disorders
• phytanic acid
• Refsum's disease