The Effect of Theophylline on Tryptophan Pyrrolase in the Hypophysectomized Rat and Some Observations on the Validity of Tryptophan Pyrrolase Assays

Abstract

Abstract Theophylline-treated rats converted [ring-2-14C]tryptophan more slowly to 14CO2 than control rats. Since 14CO2 production has been taken as an in vivo assay of tryptophan pyrrolase, this suggested a decline in enzyme activity. However, no change was found when the enzyme was measured in vitro. Because of this discrepancy the in vivo assay was investigated. The inhibition is not attributable to decreased availability of radioactive substrate or to inhibition of another enzyme on the pathway to 14CO2. This suggests that theophylline causes a decreased rate of tryptophan degradation by tryptophan pyrrolase. Theophylline might be acting by converting holoenzyme to an inactive holoenzyme form in a way that is not detected in the in vitro assay. This hypothesis is supported by the effect of a tryptophan load, which overcomes the inhibition of theophylline. The interconversion of inactive and active holoenzyme forms may be a means of regulating tryptophan pyrrolase activity.