Studies on the Metabolism of the Benzene Ring of Tryptophan in Mammalian Tissues

In preceding reports from this laboratory, a-hydroxyanthranilic acid was shown to be converted to glutaric acid and COz by crude extracts of cat liver (l-3). Evidence was also presented that ol-amino-p-carboxymuconic e-semialdehyde, the primary oxidation product of 3-hydroxyanthranilic acid by the oxygenase (4), is an obligatory intermediate in this conversion (2,3). However, all previous experiments in vitro have indicated that quinolinic acid (5) and picolinic acid (6) are the stable products thus far obtained from oc-amino-P-carboxymuconic e-semialdehyde in mammalian liver. The enzyme responsible for the formation of picolinic acid was first reported by Mehler (6) and was referred to as picolinic carboxylase (7). However, since picolinic acid was not degraded to COZ even in V&JO (7, 8), the physiological role of the enzyme as well as the metabolic pathway of a-amino@-carboxymuconic e-semialdehyde to glutaric acid have remained obscure. In this communication, we wish to describe the conversion of Lu-amino-fi-carboxymuconic e-semialdehyde to cr-aminomuconic acid catalyzed by picolinic carboxylase and a nicotinamide adenine dinucleotide-linked aldehyde dehydrogenase (Scheme 1). Since the primary product of the picolinic carboxylasecatalyzed reaction, possibly oc-aminomuconic e-semialdehyde, is extremely unstable and cyclizes rapidly to picolinic acid, oc-hydroxymuconic e-semialdehyde was employed as substrate for the purification of the dehydrogenase. The enzyme is present in the liver and kidney of several mammals and will be referred hereafter to as oc-hydroxymuconic e-semialdehyde dehydrogenase.