Tryptophan Metabolism in Humans with Various Types of Anemias

Metabolic studies were performed in a number of patients to determine the effect of anemia on tryptophan metabolism. Patients were given a tracer dose of DL-tryptophan-2-C¹⁴ or the tracer dose plus a loading dose (2 Gm.) of L-tryptophan. In those patients given the loading dose, the C¹⁴O₂ production over a 24 hour period was lower than that usually obtained in normals receiving the same dose. The loading dose did not have any significant effect on the total urinary radioactivity level. In some cases the post tryptophan loading urinary level of kynurenine, quinolinic acid, N¹-methylnicotinamide and N¹-methyl-2-pyridone-5-carboxamide were elevated. Vitamin B₆ administration returned the kynurenine and N¹-methylnicotinamide levels to normal but not the quinolinic acid or pyridone. The results obtained here indicate that in anemias the activity of the hematin dependent enzyme, tryptophan pyrrolase, was depressed as well as the enzymes converting the amino acid into CO₂. The data suggest that not only are the kynurenine catabolism enzymes vitamin B₆ dependent but that vitamin B₆ is very important to the conversion of the tryptophan metabolite 3-hydroxy-anthranilic acid into α-amino-β-carboxymuconic-ε-semialdehyde and the conversion of the semialdehyde into acetate and CO₂. In addition vitamin B₆ may be involved in the further metabolism of quinolinic acid into the pyridone.