Regulation of nuclear 3-hydroxyanthranilic acid oxidase by guanine

The oxidative dimerization 3-hydroxyanthranilic acid to cinnabarinic acid is detected in the liver nuclear fraction of a number of animal species. It is also present in nuclear fraction of various organs like the liver, kidney, spleen and thymus, although the amount of enzyme varies from organ to organ. Thymus and regenerating liver nuclei showed the least activity and this activity depends on the substrate concentration. Among the nucleic acid bases guanine offered the highest inhibition which is also competitive. The K_i for guanine for rat liver enzyme was 7 × 10⁻⁵m. Cinnabarinic acid was able to inhibit RNA synthesis by isolated nuclei. The concentration of 3 hydroxyanthranilic acid required for complete inhibition was 3 × 10⁻⁴m, 1 × 10⁻³m and 4 × 10⁻³ for rat liver, rat thymus and regenerating liver nuclear fraction, respectively; 8 × 10⁻⁴m guanine partially reverses this inhibition. The DNA isolated from rat liver nuclear fraction after reacting with 3-hydroxyanthranilic acid or cinnabarinic contained bound cinnabarinie acid. The visible spectrum of cinnabarinic acid bound to DNA was different from that of pure cinnabarinic acid.