Species Variation in the Metabolism

The establishment of 3-hydroxyanthranilate (3-OHAA) as an intermediate in the conversion of tryptophan to niacin or its biological equivalent in Neurospora (1, 2) has led to findings (3-5) which indicate that this compound serves a similar role in animals. Much effort to establish the details of the individual reactions involved has centered around studies of the products of the oxidation of 3-OHAA in vitro. In addition to niacin (NA) (3) and its end product, N1-methylnicotinamide (4, 6), quinolinic acid (&A) (7, 8) is formed from 3-OHAA in vivo. Studies with liver preparations have indicated that in some species 3-OHAA is oxidized to an unstable intermediate (Compound I) (9-11) which in turn gives rise to an almost quantitative yield of &A by a non-enzymatic process. Compound I was reported to be converted by an enzyme (L‘Enzyme II”) present in guinea pig and beef liver to another product tentatively identified as picolinic acid (PA) by RF values and ultraviolet absorption spectra (12). Subsequent experiments (13) with use of 02’s established the identity of this product as well as the general type of reaction involved in the opening of the aromatic ring. On the basis of studies which showed that 60 to 90 per cent of the carboxyl carbon of 3-OHAA was expired as CO2 (14, 15), and that little or no carboxyl carbon of labeled NA was expired by the rat, Mehler and May (15) suggested that, “This is evidence that the decarboxylation to form picolinic acid is a major step in the metabolism of 3hydroxyanthranilic acid in vivo.” This view failed to take into account the possibility of alternative pathways for the metabolism of 3-OHAA or its oxidation product (Compound I). The data which follow prove that