scholarly journals Inhibition of glutathione S-transferase by bile acids

1981 ◽  
Vol 197 (2) ◽  
pp. 321-325 ◽  
Author(s):  
D A Vessey ◽  
D Zakim
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Soluble Fraction ◽  
Transferase Activity ◽  
Glutathione S Transferase ◽  
Pig Liver ◽  
Acceptor Substrate ◽  
Competitive Inhibitors ◽  
Guinea Pig Liver ◽  
Microsomal Glutathione

The effects of bile acids on the detoxification of compounds by glutathione conjugation have been investigated. Bile acids were found to inhibit the total soluble-fraction glutathione S-transferase activity from rat liver, as assayed with four different acceptor substrates. Dihydroxy bile acids were more inhibitory than trihydroxy bile acids, and conjugated bile acids were generally less inhibitory than the parent bile acid. At physiological concentrations of bile acid, the glutathione S-transferase activity in the soluble fraction was inhibited by nearly 50%. This indicates that the size of the hepatic pool of bile acids can influence the ability of the liver to detoxify electrophilic compounds. The A, B and C isoenzymes of glutathione S-transferase were isolated separately. Each was found to be inhibited by bile acids. Kinetic analysis of the inhibition revealed that the bile acids were not competitive inhibitors of either glutathione or acceptor substrate binding. The microsomal glutathione S-transferase from guinea-pig liver was also shown to be inhibited by bile acids. This inhibition, however, showed characteristics of a non-specific detergent-type inhibition.

scholarly journals The biochemical basis for the conjugation of bile acids with either glycine or taurine

1978 ◽  
Vol 174 (2) ◽  
pp. 621-626 ◽  
Author(s):  
Donald A. Vessey
Keyword(s):  
Guinea Pig ◽  
Bile Acids ◽  
Soluble Fraction ◽  
Rabbit Liver ◽  
Supernatant Fraction ◽  
Pig Liver ◽  
Biochemical Basis ◽  
High Affinity ◽  
Guinea Pig Liver ◽  
Soluble Fractions

All animals, except for the placental mammals, conjugate their bile acids exclusively with taurine. However, in certain of the placental mammals, glycine conjugates are also found. The basis for the appearance of glycine conjugation among the placental mammals was investigated. The reaction of choloyl-CoA with glycine and taurine, as catalysed by the soluble fraction from guinea-pig liver, had a high affinity for taurine and a poor affinity for glycine. The predominant synthesis of glycine conjugates in the guinea pig can be related to the fact that guinea-pig liver contains an unusually low concentration of taurine and a high concentration of glycine. Rabbits make exclusively glycine conjugates and their livers also contain low concentrations of taurine. However, the biochemical basis for their glycine conjugation is more straightforward than in the guinea pig in that the soluble fraction from rabbit liver has a high affinity for glycine and a poor affinity for taurine. Alternative-substrate-inhibition studies with glycine and taurine in soluble fractions from guinea-pig and rabbit liver revealed that glycine and taurine were mutually inhibitory. This suggests that there is only one enzyme for glycine and taurine conjugation in these tissues. The soluble fractions from bovine liver and human liver also made both glycine and taurine conjugates and evidence is presented that suggests that there is only one enzyme in these tissues too. Even the rat, which excretes mostly taurine conjugates, could make both glycine and taurine conjugates in vitro. However, in contrast with all of the placental mammals studied, the supernatant fraction from liver of the chicken, and other non-mammals, could not make glycine conjugates even in the presence of very high concentrations of glycine.

scholarly journals Studies of endogenous inhibitors of microsomal glutathione S-transferase

1982 ◽  
Vol 207 (1) ◽  
pp. 57-64 ◽  
Author(s):  
T D Boyer ◽  
D Zakim ◽  
D A Vessey
Keyword(s):  
Microsomal Fraction ◽  
Hepatic Metabolism ◽  
Organic Layer ◽  
Transferase Activity ◽  
Glutathione S Transferase ◽  
Unilamellar Vesicles ◽  
Physiological Regulator ◽  
Liver Microsomal Fraction ◽  
Small Unilamellar Vesicles ◽  
Microsomal Glutathione

Glutathione S-transferase is present in rat liver microsomal fraction, but its activity is low relative to the transferase activity present in the soluble fraction of the hepatocyte. We have found, however, that the activity of microsomal glutathione S-transferase is increased 5-fold after treatment with small unilamellar vesicles made from phosphatidylcholine. The increase in activity is due to the removal of an inhibitor of the enzyme from the microsomal membrane. The inhibitor is present in the organic layer of a washed Folch extract of the microsomal fraction. When this fraction of the microsomal extract is reconstituted in the form of small unilamellar vesicles, it inhibits microsomal glutathione S-transferase that had been activated by prior treatment with small unilamellar vesicles of pure phosphatidylcholine, but does not affect the activity of unactivated microsomal glutathione S-transferase. The inhibitor did not seem to be formed during the isolation of the microsomal fraction, and hence may be a physiological regulator of microsomal glutathione S-transferase. In this regard, both free fatty acid (palmitate) and lysophosphatidylcholine were shown to inhibit the enzyme reversibly. The results indicate that the activity of microsomal glutathione S-transferase is far greater than appreciated until now, and that this form of the enzyme may be an important factor in the hepatic metabolism of toxic electrophiles.

Differential effects of blood insulin levels on microsomal enzyme activities from hepatic and extrahepatic tissues of male rats

1992 ◽  
Vol 70 (5) ◽  
pp. 727-731 ◽  
Author(s):  
Cristina E. Carnovale ◽  
Viviana A. Catania ◽  
Juan A. Monti ◽  
Maria C. Carrillo
Keyword(s):  
Diabetic Rats ◽  
Male Rats ◽  
Blood Levels ◽  
Transferase Activity ◽  
Glutathione S Transferase ◽  
Glucuronyl Transferase ◽  
Aniline Hydroxylase ◽  
Cytosolic Glutathione ◽  
Male Wistar Rats ◽  
Microsomal Glutathione

Microsomal glutathione S-transferase, UDP-glucuronyl transferase, and aniline hydroxylase activities were determined in liver, renal cortex, and small intestine of control, streptozotocin-diabetic, alloxan-diabetic, and untreated insulin-injected male Wistar rats. Renal microsomal glutathione S-transferase activity showed a direct linear relationship with insulin blood levels, in agreement with our previous report on cytosolic glutathione S-transferase. This result suggests a possible regulatory mechanism of insulin that needs to be further examined. The hepatic microsomal UDP-glucuronyl transferase was only decreased in streptozotocin-diabetic rats and was not restored by insulin treatment. Intestinal UDP-glucuronyl transferase exhibited an opposite response in streptozotocin-treated animals that was not normalized by the administration of insulin. Hepatic aniline hydroxylase showed the same behaviour as intestinal UDP-glucuronyl transferase. These results suggest that streptozotocin and (or) its metabolites have a direct effect on hepatic and intestinal UDP-glucuronyl transferase activity and on hepatic aniline hydroxylase activity. On the other hand, insulin regulation of enzyme activity varies from one organ to another.Key words: insulin, streptozotocin, alloxan, glutathione S-transferase, UDP-glucuronyl transferase, aniline hydroxylase.

scholarly journals Activation versus inhibition of microsomal glutathione S-transferase activity by acrolein. Dependence on the concentration and time of acrolein exposure

2017 ◽  
Vol 275 ◽  
pp. 116-120
Author(s):  
Mireille M.J.P.E. Sthijns ◽  
Gertjan J.M. den Hartog ◽  
Caterina Scasso ◽  
Jan P. Haenen ◽  
Aalt Bast ◽  
...  
Keyword(s):  
Transferase Activity ◽  
Glutathione S Transferase ◽  
Microsomal Glutathione

scholarly journals Comparison of renal and hepatic glutathione S-transferases in the rat

1976 ◽  
Vol 158 (2) ◽  
pp. 243-248 ◽  
Author(s):  
N Kaplowitz ◽  
G Clifton ◽  
J Kuhlenkamp ◽  
J D Wallin
Keyword(s):  
Organic Anion ◽  
Gel Filtration ◽  
Competitive Inhibitor ◽  
Transferase Activity ◽  
Close Correspondence ◽  
Glutathione S Transferase ◽  
Competitive Inhibitors ◽  
Liver And Kidney ◽  
Glutathione S Transferases

Renal and hepatic GSH (reduced glutathione) S-transferase were compared with respect to substrate and inhibitory kinetics and hormonal influences in vivo. An example of each of five classes of substrates (aryl, aralkyl, epoxide, alkyl and alkene) was used. In the gel filtration of renal or hepatic cytosol, an identical elution volume was found for all the transferase activities. Close correspondence in Km values was found for aryl, epoxide- and alkyl-transferase activities, with only the aralkyl activity significantly lower in kidney. Probenecid and p-aminohippurate were competitive inhibitors of renal aryl-, aralkyl-, epoxide- and alkyl-transferase activities and inhibited renal alkene activity. Close correspondence in Ki values for inhibition by probenecid of these activities in kidney and liver was found. In addition, furosemide was a potent competitive inhibitor of renal alkyl-transferase activity. Hypophysectomy resulted in significant increases in aryl-, araklyl-, and expoxide-transferase activities in liver and kidney. The hypophysectomy-induced increases in renal aryl- and aralkyl-transferase activities (approx. 100%) were more than twofold greater than increases in hepatic activities (approx. 40%). Administration of thyroxine prevented the hypophysectomy-induced increase in aryltransferase activity in both kidney and liver. The renal GSH S-transferases, in view of similarities to the hepatic activities, may play a role as cytoplasmic organic-anion receptors, as previously proposed for the hepatic enzymes.

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