Production of D-Kynurenine and Other Metabolites from D-Tryptophan by the Intact Rabbit and by Rabbit Tissue

Abstract

Use of sensitive chromatographic techniques now available for the separation of D-kynurenine has shown that, contrary to earlier negative claims, it can be produced when D-tryptophan is administered parenterally to the rabbit or when it is incubated with liver preparations. D-Kynurenine is slowly convertible to kynurenic acid, both in the intact animal and by kidney homogenates. Conversion by purified D-amino acid oxidase is also possible, probably because the α-keto analog formed through deamination undergoes ring closure spontaneously. The striking production of indolepyruvic acid from D-tryptophan in the intact rabbit favors the probability that some of the kynurenic acid excreted may have arisen via L-tryptophan formed by inversion. Feeding polished rice undoubtedly induces incipient coenzyme deficiencies, but contrary to earlier claims, it failed to increase the excretion of kynurenine. It lowered the output of kynurenic acid and enhanced moderately the production of 3-hydroxykynurenine. Tests confirmed the presence of “D-tryptophan pyrrolase” in the small intestine and its capacity to attack both D- and L-tryptophan. Liver homogenates produced less kynurenine from D- than from L-tryptophan. Enantiomorphic identities were established chromatographically and by reaction with D- and L-amino acid oxidases.