Inducible and constitutive kynureninases. Control of the inducible enzyme activity by transamination and inhibition of the constitutive enzyme by 3-hydroxyanthranilate.
The inducible kynureninase from Neurospora crassa is inactivated by incubation with L-alanine or L-ornithine. The inactivated enzyme is resolved to the apoenzyme by dialysis. Reactivation of the apoenzyme is achieved by incubation with pyridoxamine 5'-phosphate plus pyruvate, as well as with pyridoxal 5'-phosphate. The kynurenine hydrolysis proceeds linearly in the presence of added pyridoxal 5'-phosphate, or pyridoxamine 5'-phosphate plus pyruvate. These findings indicate that the fungal inducible kynureninase can act as an amino-transferase to control the enzyme activity, and that the control mechanism is similar to that reported for the bacterial kynureninase (Moriguchi, M. & Soda, K. (1973) Biochemistry 12, 2974-2980). The ratio of kynureninase activity to aminotransferase activity was determined with bacterial and fungal enzymes. All the inducible kynureninases from various fungal species examined are also controlled by the transamination. In contrast, the pig liver kynureninase and the fungal constitutive enzymes are little or not at all affected by preincubation with amino acids. Thus, the present regulatory mechanism does not operate in these constitutive-type enzymes. The rate of hydrolysis of L-3-hydroxykynurenine by the pig liver enzyme decreases with increase in the incubation time; the enzyme is inhibited by 3-hydroxyanthranilate produced from L-3-hydroxykynurenine. The inhibition is found in all the constitutive-type enzymes, suggesting that 3-hydroxyanthranilate plays a regulatory role in NAD biosynthesis from tryptophan.
D015095:3-Hydroxyanthranilic Acid / Q000494:pharmacology*; D000409:Alanine / Q000494:pharmacology; D000596:Amino Acids / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D006867:Hydrolases / Q000378:metabolism*; D007700:Kinetics; D007737:Kynurenine; D009491:Neurospora / Q000201:enzymology*; D009492:Neurospora crassa / Q000201:enzymology*; D009952:Ornithine / Q000494:pharmacology; D013045:Species Specificity; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D000596:Amino Acids; D062367:ortho-Aminobenzoates; D015095:3-Hydroxyanthranilic Acid; D007737:Kynurenine; D009952:Ornithine; D006867:Hydrolases; D000409:Alanine