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Effect of Cytoplasmic Particles on Tryptophan Pyrrolase Activity of Rat Liver

Olga Greengard 1, N. Mendelsohn 1, and G. Acs 1

From the 1 From the Institute for Muscle Disease, Inc., New York, New York 10021

An activation of tryptophan pyrrolase in vitro distinct from the previously known conversion of inactive apotryptophan pyrrolase to active holotryptophan pyrrolase by hematin or by boiled particulate fractions of liver is described. This stimulation occurs by the addition of small amounts of mitochondria or microsomes to cell sap in the presence of excess methemoglobin. The particulate activator is heat-sensitive, and its speed of action is dependent on temperature and concentration. Thus, three different levels of tryptophan pyrrolase activity can be obtained: (a) that in the absence of added cofactor, reflecting the endogenous holoenzyme; (b) that in the presence of added cofactor, reflecting the sum of endogenous holo- plus apotryptophan pyrrolase; and (c) that appearing after incubation with the mitochondria (or microsomes) plus a source of coenzyme, reflecting "latent" enzyme. In normal liver these three activities are approximately 1,2, and 5 units. In liver of rats 4 hours after administration of hydrocortisone or tryptophan the corresponding values are 4, 7, 25 and 10, 11, 12, respectively. Thus, both the substrate and the hormone raise in vivo the level of total obtainable tryptophan pyrrolase activity. The difference between the two inducers is that hydrocortisone (unless its action is prevented by the administration of actinomycin) causes the accumulation of much activity revealed only by the heat-labile particulate activator, whereas after treatment with tryptophan there is very little of such latent enzyme or of the inactive apoenzyme. Tryptophan, if administered to hydrocortisone-treated rats 1 hour before assay, converts much of the accumulated inactive enzyme to the active form.

Submitted on August 12, 1965


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K. Altman and O. Greengard
Tryptophan Pyrrolase Induced in Human Liver by Hydrocortisone: Effect on Excretion of Kynurenine
Science, January 21, 1966; 151(3708): 332 - 333.
[Abstract] [PDF]




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