Guinea-pig liver tryptophan pyrrolase. Absence of detectable apoenzyme activity and of hormonal induction by cortisol and possible regulation by tryptophan

1. When assayed in fresh homogenates, guinea-pig liver tryptophan pyrrolase exists only as holoenzyme. It does not respond to agents that activate or inhibit the rat liver enzyme in vitro. Only by aging (for 30min at 5 degrees C) does the guinea-pig enzyme develop a requirement for ascorbate. 2. The guinea-pig liver enzyme is activated by the administration of tryptophan but not cortisol, salicylate, ethanol or 5-aminolaevulinate. 3. The tryptophan enhancement of the guinea-pig liver pyrrolase activity is prevented by 0, 34 and 86% by pretreatment with actinomycin D, cycloheximide or allopurinol respectively. 4. The guinea-pig liver tryptophan pyrrolase is more sensitive to tryptophan administration than is the rat enzyme. On the other hand, the concentrations of tryptophan in sera and livers of guinea pigs are 45-52% less than those in rats. 5. It is suggested that tryptophan may regulate the activity of guinea-pig liver tryptophan pyrrolase by mobilizing a latent form of the enzyme whose primary function is the detoxication of its substrate.     

Age-related differential induction of tryptophan pyrrolase by hydrocortisone in the liver of male rats

The activity and the regulatory pattern of tryptophan pyrrolase of the liver of male rats during various phases of the life span were studied with a view to investigate the differential effectiveness of hydrocortisone in relation to growth, development, and senescence of an organism. The level of this enzyme shows no significant change till adulthood but decreases significantly thereafter with increasing age. Adrenalectomy and hydrocortisone treatments decrease and increase, respectively the activity of this enzyme significantly in rats of all the ages. However, the effects of these treatments are highest in the mature rat. Induction of the enzyme by hydrocortisone is actinomycin D-sensitive.     

Tryptophan catabolism by tryptophan pyrrolase in rat liver. The effect of tryptophan loads and changes in tryptophan pyrrolase activity.

We investigated how changes in tryptophan pyrrolase activity and tryptophan loads affect the breakdown of tryptophan was estimated by injecting rats with [ring-2-14-C]tryptophan and measuring respiratory 14-CO2. We concluded, contrary to previous reports, that induction of tryptophan pyrrolase definitely will increase the rate of tryptophan breakdown. Tryptophan loads also increase tryptophan breakdown even in circumstances where there is no increase in tryptophan pyrrolase activity, presumably by increasing the saturation of the enzyme. After a tryptophan load (50 mg per kg) the increase in liver tryptophan concentration lasts only 30 min. The rapid return of liver tryptophan to normal may be due partly to the high turnover rate of liver tryptophan. We estimate that tryptophan pyrrolase degrades tryptophan in vivo at a rate that is equivalent to the whole liver tryptophan concentration in 7.5 min or less.     

Destabilization of tyrosine aminotransferase by amino acids

Summary Several L-amino acids (tyrosine, glutamate, methionine, tryptophan, and phenylalanine) and penicillamine destabilized purified tyrosine aminotransferase by removing enzyme-bound pyridoxal 5-phosphate. The destabilization was measured as a progressive loss of enzyme activity in samples taken at intervals from a primary mixture that was incubated at 37°C. Each destabilizing amino acid either served as a substrate for this enzyme or was a product of transamination. In contrast, L-cysteine destabilized the enzyme only if liver homogenate was added, which generated polysulfide by desulfuration. Cysteine complexed free pyridoxal-5-phosphate but did not remove it from the enzyme. Other amino acids did not destabilize tyrosine aminotransferase at the concentrations tested.Abbreviations TyrAT tyrosine aminotransferase (E.C. 2.6.1.5) - PLP pyridoxal-5-phosphate     

The effect of copper deficiency of the induction of tryptophan pyrrolase in chick liver by hydrocortisone

The induction of tryptophan pyrrolase in chick liver by hydrocortisone was studied in copper- and magnesium-deficient chicks. Magnesium deficiency did not influence the induction of the enzyme, whereas copper deficiency significantly decreased it. These results suggest that tryptophan pyrrolase of chick liver, like that in Pseudomonas, is a copper-containing enzyme.