Metabolism of D- and L-Kynurenine-keto- 14 C in Rats and the Effects of Unlabeled Enantiomers ∗

Abstract

Summary

The DL-kynurenine-keto-¹⁴C was resolved by chromatography on powdered paper columns. Rats were injected intraperitoneally with aqueous solutions of a ¹⁴C-isomer either alone, or together with an equimolar amount of unlabeled enantiomer, or 30 min after a loading dose of the enantiomer. Respiratory and urinary radioactivities were measured. Urinary quinolinic acid, nicotinic acid, kynurenic acid, xanthurenic acid, kynurenine, hydroxykynurenine, and N'-methylnicotinamide were isolated by carrier techniques and their radioactivity was measured. The L-kynurenine-¹⁴C was more rapidly metabolized to ¹⁴CO₂ than was the D-isomer and was also a better precursor of quinolinic acid. Only traces of label appeared in nicotinic acid and there seen in approximately equal amounts in each isomer. A load of D-isomer inhibited the metabolism of the L-¹⁴C-isomer to ¹⁴CO₂ and on the basis of changes in urinary metabolites, it is suggested that D-kynurenine inhibits L-kynurenine hydroxylation. A load of the L-isomer increased the metabolism of the D-¹⁴C-isomer very slightly. Kynurenic acid was the main product of D-kynurenine-¹⁴C metabolism identified in the urine. This could arise by deamination and cyclization as a result of the action of a transaminase or D-amino acid oxidase. Other urinary metabolites were also labeled from D-kynurenine-¹⁴C, indicating further metabolism of this isomer without conversion to the L-form. The appearance of label from D-kynurenine-¹⁴C in niacin metabolites indicates the presence of metabolic pathways in the rat capable of converting D-kynurenine to this vitamin.