The regulation of rat liver tryptophan pyrrolase activity by reduced nicotinamide-adenine dinucleotide (phosphate). Experiments with glucose and nicotinamide

1. Chronic administration of glucose or nicotinamide in drinking water inhibits the activity of rat liver tryptophan pyrrolase, and subsequent withdrawal causes an enhancement. The enzyme activity is also inhibited by administration in drinking water of sucrose, but not fructose, which is capable of preventing the glucose effect. 2. The inhibition by glucose or nictinamide is not due to a defective apoenzyme synthesis nor a decreased cofactor availability. 3. The inhibition by nicotinamide is reversed by regeneration of liver NAD+ and NADP+ in vivo by administration of fructose, pyruvate or phenazine methosulphate. Inhibition by glucose is also reversed by the above agents and by NH4Cl. Reversal of inhibition by glucose or nicotinamide is also achieved in vitro by addition of NAD+ or NADP+. 4. Glucose or nicotinamide increases liver [NADPH]. [NADP+] is also increased by nicotinamide. [NADPH] is also increased by sucrose, but not by fructose, which prevents the glucose effect. Phenazine methosulphate prevents the increase in [NADPH] caused by both glucose and nicotinamide. 5. It is suggested that the inhibition of tryptophan pyrrolase activity by glucose or nicotinamide is mediated by both NADPH and NADH.

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The effects of acute and chronic nicotine hydrogen (+)-tartrate administration and subsequent withdrawal on rat liver tryptophan pyrrolase activity and their comparison with those of morphine, phenobarbitone and ethanol

Biochemical Journal ◽

10.1042/bj1480425 ◽

1975 ◽

Vol 148 (3) ◽

pp. 425-432 ◽

Cited By ~ 6

Author(s):

A A Badawy ◽

M Evans

Keyword(s):

Rat Liver ◽

Acute Administration ◽

Nicotine Treatment ◽

Chronic Nicotine ◽

Nicotine Administration ◽

Hormonal Mechanism ◽

Tryptophan Pyrrolase ◽

Subsequent Withdrawal

Acute administration of nicotine hydrogen (+)-tartrate enhances the activity of rat liver tryptophan pyrrolase by a hormonal mechanism. Chronic nicotine treatment inhibits, and subsequent withdrawal enhances, the pyrrolase activity. The inhibition during chronic treatment is not due to a defective apoenzyme synthesis nor a decreased cofactor availability. Regeneration of liver NADP+ in vitro and in vivo reverses the inhibition. Chronic nicotine administration increases the liver NADPH concentration. The above effects of nicotine resemble to a remarkable degree those previously shown for morphine, phenobarbitone and ethanol. All effects are compared, and their possible significance in relation to drug dependence is discussed.

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EFFECTS OF CHRONIC ADMINISTRATION AND SUBSEQUENT WITHDRAWAL OF ETHANOL-CONTAINING LIQUID DIET ON RAT LIVER TRYPTOPHAN PYRROLASE AND TRYPTOPHAN METABOLISM

Alcohol and Alcoholism ◽

10.1093/oxfordjournals.alcalc.a008133 ◽

1996 ◽

Vol 31 (2) ◽

pp. 205-215 ◽

Cited By ~ 8

Author(s):

S. BANO ◽

R. G. ORETTI ◽

C. J. MORGAN ◽

A. A.-B. BADAWY ◽

P. R. BUCKLAND ◽

...

Keyword(s):

Rat Liver ◽

Chronic Administration ◽

Liquid Diet ◽

Tryptophan Metabolism ◽

Tryptophan Pyrrolase ◽

Subsequent Withdrawal

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Tryptophan pyrrolase in haem regulation. The relationship between the depletion of rat liver tryptophan pyrrolase haem and the enhancement of 5-aminolaevulinate synthase activity by 2-allyl-2-isopropylacetamide

Biochemical Journal ◽

10.1042/bj1860763 ◽

1980 ◽

Vol 186 (3) ◽

pp. 763-772 ◽

Cited By ~ 13

Author(s):

A A B Badawy ◽

C J Morgan

Keyword(s):

Rat Liver ◽

Activity Maximum ◽

Haem Biosynthesis ◽

Hexobarbital Sleeping Time ◽

Tryptophan Pyrrolase ◽

Liver Homogenates ◽

The Relationship ◽

Cytochrome P 450 ◽

Phenazine Methosulphate

Rat liver tryptophan pyrrolase haem is maximally depleted at 30 min after administration of a 400 mg/kg dose of 2-allyl-2-isopropylacetamide. This depletion lasts for 24 h, by which time 5-aminoleevulinate synthase activity becomes maximally enhanced. 2. though the above maximum depletion of pyrrolase haem (at 0.5h) is also produced by a 100 mg/kg dose of the porphyrogen, this does not enhance synthase activity at 24 h. It and smaller doses, however, cause a smaller but earlier enhancement of synthase activity (maximum at 2 h) and produce a similarly short-lived deplation of pyrrolase haem. 3. The depletion of pyrrolase haem and the enhancement of synthase activity by the porphyrogen are inhibited by compound SKF 525-A and phenazine methosulphate, and are potentiated by nicotinamide but not by phenobarbitone. Phenazine methosulphate and nicotinamide also exert opposite effects on hexobarbital sleeping-time. 4. 2-Allyl-2-isopropylacetamde also the depletes pyrrolase haem in vitro. It does so in liver homogenates of control rats in the presence, and in those of phenobarbitone-treated rats in the absence of added NADPH. 5. A discussion of the present results in relation to previous work with other haemoproteins suggests that, whereas cytochrome P-450 (haem) is primarily involved in the production of the active (porphyrogenic) metabolite(s) of 2-allyl-2-isopropylacetamide, the haem pool used by tryptophan pyrrolase may play an important role in the effects of this compound on haem biosynthesis.

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Studies of the Stability in Vivo and in Vitro of Rat Liver Tryptophan Pyrrolase

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)96999-1 ◽

1965 ◽

Vol 240 (12) ◽

pp. 4609-4620 ◽

Cited By ~ 16

Author(s):

Robert T. Schimke ◽

E.W. Sweeney ◽

C.M. Berlin

Keyword(s):

Rat Liver ◽

Tryptophan Pyrrolase ◽

The Stability

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The role of liver tryptophan pyrrolase in the opposite effects of chronic administration and subsequent withdrawal of drugs of dependence on rat brain tryptophan metabolism

Biochemical Journal ◽

10.1042/bj1960161 ◽

1981 ◽

Vol 196 (1) ◽

pp. 161-170 ◽

Cited By ~ 18

Author(s):

A A Badawy ◽

N F Punjani ◽

M Evans

Keyword(s):

Chronic Administration ◽

Tryptophan Metabolism ◽

Chronic Morphine ◽

Drug Induced ◽

Tryptophan Pyrrolase ◽

Subsequent Withdrawal ◽

Induced Changes ◽

Phenazine Methosulphate ◽

The Brain

1. Chronic administration of morphine, nicotine or phenobarbitone has previously been shown to inhibit rat liver tryptophan pyrrolase activity by increasing hepatic [NADPH], whereas subsequent withdrawal enhances pyrrolase activity by a hormonal-type mechanism. 2. It is now shown that this enhancement is associated with an increase in the concentration of serum corticosterone. 3. Chronic administration of the above drugs enhances, whereas subsequent withdrawal inhibits, brain 5-hydroxytryptamine synthesis. Under both conditions, tryptophan availability to the brain is altered in the appropriate direction. 4. The chronic drug-induced enhancement of brain tryptophan metabolism is reversed by phenazine methosulphate, whereas the withdrawal-induced inhibition is prevented by nicotinamide. 5. The chronic morphine-induced changes in liver [NADPH], pyrrolase activity, tryptophan availability to the brain and brain 5-hydroxytryptamine synthesis are all reversed by the opiate antagonist naloxone. 6. It is suggested that the opposite effects on brain tryptophan metabolism of chronic administration and subsequent withdrawal of the above drugs of dependence are mediated by the changes in liver tryptophan pyrrolase activity. 6. Similar conclusions based on similar findings have previously been made in relation to chronic administration and subsequent withdrawal of ethanol. These findings with all four drugs are briefly discussed in relation to previous work and the mechanism(s) of drug dependence.

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The effects of salicylate on the activity of rat liver tryptophan pyrrolase in vitro and in vivo

Biochemical Journal ◽

10.1042/bj1230171 ◽

1971 ◽

Vol 123 (2) ◽

pp. 171-174 ◽

Cited By ~ 14

Author(s):

A. A.-B. Badawy ◽

M. J. H. Smith

Keyword(s):

Enzyme Activity ◽

Rat Liver ◽

Binding Sites ◽

Actinomycin D ◽

Sodium Salicylate ◽

Progressive Increase ◽

Tryptophan Pyrrolase ◽

Enzyme Ratio

1. Salicylate, in concentrations of 0.05mm and above, inhibits the basal activity of tryptophan pyrrolase in homogenates of rat liver and the activity induced by cortisol but not that induced by tryptophan. The inhibition is abolished by adding haematin to the reaction mixtures. 2. The intraperitoneal injection of 400mg of sodium salicylate/kg in the rat causes a decrease in the tryptophan pyrrolase activity in the liver at 30min, the activity is restored to normal at 2h, increases to sixfold after 5h and returns to the basal value at 12h. The activation of the enzyme by salicylate is prevented by the administration of cycloheximide but not by pretreatment with actinomycin D. The effects of the combined injection of salicylate and cortisol are additive, whereas those of salicylate plus tryptophan are not. The injection of salicylate causes a progressive increase in the holo-/apo-enzyme ratio and an increased content of tryptophan in the liver over a period of 3h. 3. It is suggested that salicylate inhibits tryptophan pyrrolase activity in vitro and in vivo by interacting with iron protoporphyrins and causes a later enhancement of the enzyme activity in vivo by a mechanism involving the release of tryptophan from its binding sites on circulating albumin and on other proteins.

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