scholarly journals The effects of acetate, metal cations, phenobarbitone, porphyrogens and substrates of glycine acyltransferase on the utilization of haem by rat liver apo-(tryptophan pyrrolase)

1977 ◽  
Vol 164 (2) ◽  
pp. 431-438 ◽  
Author(s):  
A A B Badawy
Keyword(s):  
Enzyme Activity ◽  
Rat Liver ◽  
Metal Cations ◽  
Oxygenase Activity ◽  
Tryptophan Pyrrolase ◽  
Haem Oxygenase ◽  
Activity Enhancement

1. The utilization of haem by rat liver apo-(tryptophan pyrrolase) under basal conditions and after enhancement of the enzyme activity by various mechanisms was studied under the influence of treatments affecting various aspects of liver haem metabolism. 2. These treatments were: benzoate and p-aminobenzoate as substrates of glycine acyltransferase, acetate as an inhibitor of 5-aminolaevulinate synthase activity, enhancement of 5-aminolaevulinate dehydratase by aluminium, destruction of haem and inhibition of ferrochelatase by porphyrogens, increased haem utilization by phenobarbitone and enhancement of haem oxygenase activity by metal cations. 3. The results show that the haem saturation of the apoenzyme is sensitive to all these treatments. 4. The possible usefulness of tryptophan pyrrolase in studying the regulation of liver haem is suggested.

scholarly journals Effect of endotoxin on tryptophan pyrrolase and delta-aminolaevulinate synthase: evidence for an endogenous regulatory haem fraction in rat liver

1977 ◽  
Vol 166 (2) ◽  
pp. 301-304 ◽  
Author(s):  
D M Bissell ◽  
L E Hammaker
Keyword(s):  
Rat Liver ◽  
Peak Activity ◽  
Endotoxin Administration ◽  
Oxygenase Activity ◽  
Tryptophan Pyrrolase ◽  
Haem Oxygenase ◽  
Enzyme Functions ◽  
New Evidence ◽  
Cytochrome P 450

Endotoxin was administered to rats at a dose shown previously to stimulate hepatic haem oxygenase activity and to block induction of delta-aminolaevulinate synthase, apparently by causing redistribution of haem from cytochrome P-450 to a regulatory haem pool in the liver. Within 5h of the administration of endotoxin (at a time when the effect of the compound on cytochrome P-450 is maximal) the relative saturation of tryptophan pyrrolase with intrinsic haem rose, from a basal value of 50% to 90%, indicating that ‘free’ haem had become available. Concurrently, the activity of delta-aminolaevulinate synthase was decreased to 25% of its basal value. Haem oxygenase reached peak activity 13h after endotoxin administration. These findings provide new evidence for the existence of an ‘unassigned’ hepatic haem fraction, which exchanges with cytochrome P-450 haem and regulates these three enzyme functions.

scholarly journals Phenylhydrazine-mediated induction of haem oxygenase activity in rat liver and kidney and development of hyperbilirubinaemia. Inhibition by zinc-protoporphyrin

1984 ◽  
Vol 217 (2) ◽  
pp. 409-417 ◽  
Author(s):  
M D Maines ◽  
J C Veltman
Keyword(s):  
Rat Liver ◽  
Zinc Protoporphyrin ◽  
Serum Total Bilirubin ◽  
Potent Inducer ◽  
Oxygenase Activity ◽  
Liver And Kidney ◽  
Haem Oxygenase ◽  
Cytochrome P 450

Phenylhydrazine was found to be a potent inducer of microsomal haem oxygenase activity in rat liver and kidney, but not in spleen. The phenylhydrazine-mediated increase in haem oxygenase activity was time-dependent. Maximum activity was attained 12h after treatment in the liver, and 24h after treatment in the kidney. The increases in the activity of haem oxygenase in the liver and the kidney could be inhibited by cycloheximide. Furthermore, the increases could not be elicited by the treatment of microsomal preparations in vitro with phenylhydrazine. In consonance with the increased haem oxygenase activity, a marked increase (16-fold) was observed in the serum total bilirubin concentration in phenylhydrazine-treated rats. The mechanism of haem degradation promoted by phenylhydrazine in vivo appears to differ from that in vitro; only in the former case is bilirubin formed as the end-product of haem degradation. When rats were given zinc-protoporphyrin (40 mumol/kg) 12h before and after phenylhydrazine treatment, the phenylhydrazine-mediated increases in haem oxygenase activity in the liver and the kidney were effectively blocked. Treatment of rats in vivo with the metalloporphyrin also inhibited the activity of splenic haem oxygenase, and promoted a major decrease in the serum bilirubin levels. In phenylhydrazine-treated animals, the microsomal content of cytochrome P-450 was significantly decreased in the absence of a decrease in the microsomal haem concentration. The decrease in cytochrome P-450 content was accompanied by an increased absorption in the 420nm region of the reduced CO-difference spectrum, suggesting the conversion of the cytochrome to an inactive form. The marked depletion of cellular glutathione levels suggests that this conversion may be related to the action of active intermediates and free radicals formed in the course of the interaction of phenylhydrazine with the haem moiety of cytochrome P-450.

scholarly journals Defective utilization of haem in selenium-deficient rat liver

1983 ◽  
Vol 214 (1) ◽  
pp. 53-58 ◽  
Author(s):  
M A Correia ◽  
R F Burk
Keyword(s):  
Rat Liver ◽  
Selenium Deficiency ◽  
Oxygenase Activity ◽  
Haem Oxygenase ◽  
Rapid Stimulation ◽  
Normal Controls ◽  
Stimulation Of

We have previously suggested that an inherent defect in hepatic haem utilization was responsible for the rapid stimulation of hepatic microsomal haem oxygenase activity observed in selenium-deficient rats given phenobarbital, a well known inducer of haem formation. To test this hypothesis, hepatic haem content was deliberately raised in selenium-deficient rats by administration of either tryptophan or allylisopropylacetamide, or by injecting haem itself. We now report that selenium-deficient rats are apparently relatively less efficient in utilizing hepatic haem than normal controls. The findings detailed in the present paper thus indicate that stimulation of hepatic microsomal haem oxygenase activity is indeed a manifestation of abnormal haem utilization in selenium deficiency. This suggests a novel role for selenium in hepatic haem metabolism.

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

1971 ◽  
Vol 123 (2) ◽  
pp. 171-174 ◽  
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.

scholarly journals The effects of chronic phenobarbitone administration and subsequent withdrawal on the activity of rat liver tryptophan pyrrolase and their resemblance to those of ethanol

1973 ◽  
Vol 135 (3) ◽  
pp. 555-557 ◽  
Author(s):  
Abdulla A.-B. Badawy ◽  
Myrddin Evans
Keyword(s):  
Enzyme Activity ◽  
Rat Liver ◽  
Chronic Ethanol ◽  
Ethanol Administration ◽  
Ethanol Inhibition ◽  
Chronic Ethanol Administration ◽  
Tryptophan Pyrrolase ◽  
Subsequent Withdrawal

Chronic phenobarbitone administration inhibits the apo-(tryptophan pyrrolase) activity in homogenates of rat liver and subsequent withdrawal enhances the enzyme activity by 2.5-fold. Similar effects have been previously produced by chronic ethanol administration and withdrawal, but, whereas NADH may cause the ethanol inhibition, that by phenobarbitone may be mediated by NADPH.

scholarly journals Effect of Cytoplasmic Particles on Tryptophan Pyrrolase Activity of Rat Liver

1966 ◽  
Vol 241 (2) ◽  
pp. 304-308
Author(s):  
Olga Greengard ◽  
N. Mendelsohn ◽  
G. Acs
Keyword(s):  
Rat Liver ◽  
Tryptophan Pyrrolase

Effect of saturated fat diets on rat liver NADP-linked enzymes

1965 ◽  
Vol 209 (4) ◽  
pp. 773-780 ◽  
Author(s):  
Helen M. Tepperman ◽  
Jay Tepperman
Keyword(s):  
Fatty Acids ◽  
Enzyme Activity ◽  
Rat Liver ◽  
Corn Oil ◽  
Saturated Fat ◽  
Coconut Oil ◽  
Liver Slices ◽  
Fat Diets ◽  
Effect Of Feeding

The aggregate hexosemonophosphate dehydrogenase (HMPD) activity was found to be higher in livers of rats fed a diet containing saturated fat (hydrogenated coconut oil = H) for 7 days and fasted for 48 hr than it was in similarly prepared animals fed a corn oil (CO) diet. Later, a liver HMPD-increasing effect of feeding H was found in nonfasted animals. Lipogenesis (i.e., the incorporation of acetate-1-C14 into fatty acids by liver slices) was shown to be as low or lower in the H group as in the CO. Liver slices prepared from H and CO diet adapted rats were incubated with either acetate-1-C14 or palmitate-1-C14 and the extent of incorporation of C14 into individual fatty acids was measured. With both substrates more radioactivity was found in 16:1, 18:0, and 18:1 in the case of H-fed animals. It is proposed that a component of the signal for eliciting increased NADP-linked enzyme activity in the H rats was an increased rate of oxidation of NADPH attendant on monoene formation and chain lengthening.

scholarly journals Biphasic effect of acute ethanol administration on rat liver tyrosine-2-oxoglutarate aminotransferase activity

1980 ◽  
Vol 186 (3) ◽  
pp. 755-761 ◽  
Author(s):  
A A B Badawy ◽  
B M Snape ◽  
M Evans
Keyword(s):  
Enzyme Activity ◽  
Rat Liver ◽  
Actinomycin D ◽  
Tyrosine Aminotransferase ◽  
Ethanol Metabolism ◽  
Ethanol Administration ◽  
Aminotransferase Activity ◽  
Biphasic Effect ◽  
Initial Decrease ◽  
Acute Ethanol

1. Acute ethanol administration causes a biphasic change in rat liver tyrosine aminotransferase activity. 2. The initial decrease is significant with a 200 mg/kg dose of ethanol, is prevented by adrenoceptor-blocking agnets and by reserpine, but not by inhibitors of ethanol metabolism, and exhibits many of the characteristics of the inhibition caused by noradrenaline. 3. The subsequent enhancement of the enzyme activity by ethanol is not associated with stabilization of the enzyme, but is sensitive to actinomycin D and cycloheximide. 4. It is suggested that the initial decrease in aminotransferase activity is caused by the release of catecholamines, whereas the subsequent enhancement may be related to the release of glucocorticoids.

scholarly journals Induction of carnitine acetyltransferase by clofibrate in rat liver

1981 ◽  
Vol 194 (1) ◽  
pp. 249-255 ◽  
Author(s):  
B Mittal ◽  
C K R Kurup
Keyword(s):  
Protein Synthesis ◽  
Enzyme Activity ◽  
Rat Liver ◽  
Time Lag ◽  
Mitochondrial Protein ◽  
Carnitine Acetyltransferase ◽  
Enzyme Protein ◽  
General Protein Synthesis ◽  
Liver And Kidney ◽  
General Protein

Administration of the anti-hypercholesterolaemic drug clofibrate to the rat increases the activity of carnitine acetyltransferase (acetyl-CoA-carnitine O-acetyltransferase, EC 2.3.1.7) in liver and kidney. The drug-mediated increase in enzyme activity in hepatic mitochondria shows a time lag during which the activity increases in the microsomal and peroxisomal fractions. The enzyme induced in the particulate fractions is identical with one normally present in mitochondria. The increase in enzyme activity is prevented by inhibitors of RNA and general protein synthesis. Mitochondrial protein-synthetic machinery does not appear to be involved in the process. Immunoprecipitation shows increased concentration of the enzyme protein in hepatic mitochondria isolated from drug-treated animals. In these animals, the rate of synthesis of the enzyme is increased 7-fold.

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