Tryptophan pyrrolase

Examples include the liver enzymes, homogentisate dioxygenase (oxidase) and 3-hydroxyantliranilate dioxygenase (oxidase), that contain iron and L-trypto-phan dioxygenase (tryptophan pyrrolase) (Chapter 30), that utilizes heme. 

Various minor hematological effects have been noted in animals. Rats exposed to 50-800 ppm of trichloroethylene continuously for 48 or 240 hours showed time- and dose-related depression of delta-aminolevulinate dehydratase activity in liver, bone marrow, and erythrocytes (Fujita et al. 1984 Koizumi et al. 1984). Related effects included increased delta-aminolevulinic acid (ALA) synthetase activity, reduced heme saturation of tryptophan pyrrolase and reduced cytochrome P-450 levels in the liver and increased urinary excretion of... 

Oxygenation and hydroxylation of a wide variety of biological materials almost always involves the participation of a metal ion, usually iron and sometimes copper. In one unique case, tryptophane pyrrolase, the iron is present as heme (75). The only dioxygenase enzyme reaction in which a metal ion has not been implicated is one involved in the degradation of vitamin B6 (16). 

Badawy AA-B and Evans M (1982). Inhibition of rat liver tryptophan pyrrolase and elevation of brain tryptophan concentrations by acute administration of small doses of antidepressants. British Journal of Pharmacology, 77, 59-67. 

Structure and use of porphyrins Porphyrins are cyclic compounds that readily bind metal ions—usually Fe2+ or Fe3+ The most prevalent metalloporphyrin in humans is heme, which is found in hemoglobin, myoglobin, cytochromes, and the enzymes catalase and tryptophan pyrrolase. 

The primary catabolic pathway for tryptophan in animal cells is initiated (step a, Fig. 25-11) by tryptophan 2,3-dioxygenase (tryptophan pyrrolase ... 

The focus of this chapter is the reaction site of oxygenases (hemo-proteins) having heme as the prosthetic group. We discuss the oxygen activation in tryptophan pyrrolase (TPO) and cytochrome P-450 based on our experimental results using iron-porphyrin complexes as the model for the active site of these enzymes. 

Tryptophan Pyrrolase Model Reaction and Activation of Oxygen... 

Liver tryptophan pyrrolase does not function, inducing excess conversion of tryptophan to serotonin. 

Altman K and Greengard O (1966) Correlation of kynurenine excretion with liver tryptophan pyrrolase levels in disease and after hydrocortisone induction. Journal of... 

Badawy AA (1977) The functions and regulation of tryptophan pyrrolase. Life Sciences 21,755-68. 

Badawy AA and Evans M (1975) Regulation of rat liver tryptophan pyrrolase by its cofactor haem experiments with haematin and 5-aminolaevulinate and comparison with the substrate and hormonal mechanisms. Biochemical Journal 150, 511-20. 

The first enzyme of the pathway, tryptophtm dioxygenase (edso known as tryptophan oxygenase or tryptophan pyrrolase), is rate -limiting under normal conditions. In isolated hepatocytes, the control coefficient for flux through the pathway of tryptophan dioxygenase is 0.75 tmd that for tryptophan upttike into the cells is 0.25 (Salter et til., 1986). 

Kim JH and Miller LL (1969) The functional significance of changes in activity of the enzymes, tryptophan pyrrolase and tyrosine transaminase, after induction in intact rats and in the isolated, perfused rat liver./owma/ of Biological Chemistry 244,1410-16. 

I.I. Newborn. It is known that some mammalian enzymes are absent in fetal life or may display a low activity only at the end of gestation whereas after birth their activity is enhanced to adult levels more or less rapidly. This is the case with tryptophan pyrrolase, a liver enzyme catalyzing the conversion of tryptophan to N -formylkynurenine, the first step of the kynurenine pathway. 

Tryptophan pyrrolase activity is lacking in fetal liver of rat and rabbit and appears late in gestation in the guinea pig. In the fetus and newborn of these animals the metabolism of tryptophan to nicotinic acid is decreased or completely absent (Nl). 

This fact has been explained (V4) in different ways. One possibility is that tryptophan pyrrolase is more active in the growing organism than in the adult. An accumulation of kynurenine can also be the result of relative insufiSciency of the later steps of enzyme activity in the kynuren-ine-nicotinic acid chain. 

The results obtained (M8) suggest that a defective transport of tryptophan is established across the cells of the jejunum and across the proximal renal tubules. The reduced conversion of tryptophan to kynurenine is probably due to a deficiency of tryptophan pyrrolase or to a lower transport of substrate to the enzyme. According to the same authors (M8), the cerebellar ataxia may be ascribable to intoxication by retained indolic acids. 

It has been suggested that there may be some benefit of using tryptophan in selected patients, particularly those with psychomotor retardation (3). Unfortunately, most of these reports have appeared as letters to the editors of journals (4-6) or as preliminary communications (7). In addition to the possible absence of any consistent effect, there are many plausible reasons to explain the variabihty in response. Tryptophan has been given in both the racemic and monomeric (levorotatory) forms, both alone and together with a number of substances intended to increase the synthesis or availability of serotonin, including monoamine oxidase (MAO) inhibitors (8), potassium or carbohydrate supplements (9), and co-enzymes such as pyridoxine or ascorbic acid (10). It has also been suggested that tryptophan plasma concentrations have a therapeutic window (4), and that repeated administration induces hepatic tryptophan pyrrolase, resulting in lowered plasma concentrations and loss of therapeutic effect after 2 weeks of treatment (8). Attempts have been made to amehorate this problem by coadministration of nicotinamide (4). 

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