Kynurenine metabolism in vitamin-B-6-deficient rat liver after tryptophan injection

Abstract

Tryptophan contents of liver, serum and kidney were determined in normal and vitamin-B-6-deficient rats after tryptophan injection. Tryptophan contents of normal and B-6-deficient liver were different, but not those in serum and kidney. Both kynurenine and 3-hydroxykynurenine accumulated in B-6-deficient liver more than in the normal. The 3-hydroxykynurenine contents after tryptophan injection (30 mg/100 g body wt.) increased to 1380 nmol/g of liver at 1-1.5 h, a value sufficient to produce xanthurenate, in view of the Km value of kynurenine aminotransferase. The enzymes metabolizing kynurenine were assayed at various times after tryptophan injection. The activity of kynureninase holoenzyme in B-6-deficient liver was much decreased, but the activity of total enzyme was not changed. It appeared that a high dose of tryptophan in B-6-deficient rats could cause a greater deficiency of pyridoxal 5-phosphate. Tryptophan metabolism in B-6-deficient rat liver after tryptophan administration is discussed.

Kynurenine metabolism and xanthurenic acid formation in vitamin B6-deficient rat after tryptophan injection.

“…Stanley et al (25) reported that the control strength of kynureninase in B6-deficient liver cell was higher than that of tryptophan 2, 3-dioxygenase . As we showed previously, excess tryptophan injection to B6-deficient rat led to the accumulation of a large quantity of kynurenine and 3-hydroxykynurenine in liver (6) . These indicated that liver metabolized tryptophan extremely and released its metabolites , especially kynurenine and 3-hydroxykynurenine, to the blood.…”

“…Therefore, these seemed to cause the apparent increase of saturation level with pyridoxal phosphate in B6-deficient kidney after tryptophan injection. Moreover, the effects of tryptophan adminis tration on the activities of normal kidney kynureninase and B6-deficient kidney mitochondrial kynurenine aminotransferase were different from those in the liver (6). Although the reason for these differences is unknown, the responsiveness to tryptophan injection seemed to be different between liver and kidney.…”

“…Activities of kynureninase After tryptophan injection, total activities that were determined with the addition of pyridoxal phosphate decreased, and normal kynureninase holoenzyme activity increased statistically, but B6-deficient holoenzyme activity was unchanged ( Table 2). The kynureninase activity in rat kidney cytosol was very low compared with that in liver cytosol, and saturation level of normal kidney kynureninase with pyridoxal phosphate was half that in liver enzyme (6). Moreover, the decrease of saturation level with pyridoxal phosphate observed in B6-deficient liver enzyme after tryptophan injection could not be detected in B6-deficient kidney enzyme .…”

“…Therefore, kynurenine and 3-hydroxykynurenine accumulated in the B6-deficient kidney seemed to be mainly derived from blood in addition to small amounts of their de novo synthesis. Total kynureninase activity in both normal and B6-deficient kidney was decreased and the holoenzyme activity in B6-deficient kidney was unchanged by tryptophan injection, while normal liver kynureninase activities were increased and B6-deficient liver holoenzyme activity was decreased exactly (6). The decrease in total kynureninase activity in B6-deficient kidney seemed to be caused by the strong substrate inhibition in the presence of a high concentration of 3-hydroxykynurenine in assay mixture (21).…”

“…We have previously shown that in B6-deficient rat kynurenine and 3 -hydroxykynurenine were heavily accumulated after tryptophan injection and there was a possibility of producing xanthurenic acid in liver in view of the Km values of kynurenine aminotransferase, and the activities of kynureninase were further decreased (6), probably by the xanthurenic acid accumulated (7).…”