Activation of Liver Tryptophan Oxygenase by Adenosine 3′,5′-Phosphate and by Other Purine Derivatives

Abstract

Abstract The latent form of tryptophan oxygenase (EC 1.13.1.12), which can be demonstrated in the soluble supernatant of liver through the addition of adenosine 3',5'-phosphate or other purine derivatives, differs from the form which is activated by the addition of hematin, the prosthetic group of this enzyme. Adenosine 3',5'-phosphate has to be converted to hypoxanthine in order to act as an activator. Theophylline, which blocks the cleavage of this nucleotide, prevents the activation, as does adenosine triphosphate. Xanthine oxidase, also present in the soluble rat liver preparations, serves to activate tryptophan oxygenase in the presence of its substrate hypoxanthine, which is formed from adenosine 3',5'-phosphate or from other purine derivatives. 4-Hydroxypyrazolo[3,4-d]pyrimidine (allopurinol), an inhibitor of xanthine oxidase, blocks the activation of tryptophan oxygenase by adenosine 3',5'-phosphate or by other purine derivatives, including hypoxanthine. This inhibitor inhibits the tryptophan oxygenase activity in the whole liver homogenates and prevents the activating effect of liver cytoplasmic particles in the soluble liver preparations. Catalase reduces the activation of tryptophan oxygenase by hypoxanthine, indicating probable participation of hydrogen peroxide in the activation effect of the purines via xanthine oxidase. Uric acid, the other product of the xanthine oxidase reaction, does not exhibit any activating effect.