The metabolism of l-tryptophan by liver cells prepared from adrenalectomized and streptozotocin-diabetic rats

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Abstract
The metabolism of L-tryptophan by liver cells prepared from fed normal, adrenalectomized and streptozotocin-diabetic rats was studied. At physiological concentrations (0.1 mM), the rate of oxidation of tryptophan by tryptophan 2,3-dioxygenase was 3-fold greater in liver cells from diabetic rats than in those from fed rats. In liver cells from diabetic rats, oxidation of tryptophan to CO2 and metabolites of the glutarate pathway was increased 7-fold. Quinolinate synthesis was decreased by 50%. These findings are consistent with an increase in picolinate carboxylase activity. Rates of metabolism of 0.1 mM tryptophan by hepatocytes from fed and adrenalectomized rats were similar. In all 3 types of cell preparation, fluxes through tryptophan 2,3-dioxygenase with 2.5 mM tryptophan were 7-fold greater than those obtained with 0.1 mM tryptophan. Tryptophan 2,3-dioxygenase and kynureninase fluxes in hepatocytes from fed and adrenalectomized rats were comparable, whereas those in liver cells from diabetic rats were increased 2.5-fold and 3.3-fold, respectively. Picolinate carboxylase activities of liver cells from diabetic rats were 15-fold greater than those of cells from fed rats, but rates of quinolinate synthesis were unchanged. Adrenal corticosteroids apparently are not required for the maintenance of basal activities of the kynurenine pathway, whereas chronic insulin deficiency produces changes in both the rate of oxidation and metabolic fate of tryptophan carbon.