Stable isotope studies of phytanic acid α-oxidation: in vivo production of formic acid

Abstract

The aim of this study was to test whether formate is formed during α-oxidation of phytanic acid in humans. To a healthy volunteer, [1-¹³C]phytanic acid was given as an oral substrate in a dose of 15 mg/kg body weight, after which plasma, urine and breath air samples were collected during 35 h. The plasma concentrations of [1-¹³C]phytanic acid, 2-hydroxy[1-¹³C]phytanic acid, pristanic acid and [¹³C]formate were analysed. The [1-¹³C]phytanic acid concentration increased within 5–7 h to 105 μmol/l, then decreased. Formation of 2-hydroxy[1-¹³C]phytanic acid increased during the first 11 h after which it decreased during the next 20 h. Pristanic acid increased slightly during the test. In breath air, ¹³CO₂ enrichment was measured, showing a cumulative output of ca. 30% of the ingested dose after 35 h. In both urine and plasma, enrichment of [¹³C]formate, higher than that of ¹³CO₂ was demonstrated.

These findings show that formate is a decarboxylation product in the α-oxidation of phytanic acid in vivo.