Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1982 Oct 1;207(1):57–64. doi: 10.1042/bj2070057

Studies of endogenous inhibitors of microsomal glutathione S-transferase.

T D Boyer, D Zakim, D A Vessey
PMCID: PMC1153823  PMID: 7181862

Abstract

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.

Full text

PDF
57

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beatty P. W., Reed D. J. Involvement of the cystathionine pathway in the biosynthesis of glutathione by isolated rat hepatocytes. Arch Biochem Biophys. 1980 Oct 1;204(1):80–87. doi: 10.1016/0003-9861(80)90009-0. [DOI] [PubMed] [Google Scholar]
  2. Boyer T. D., Zakim D., Vessey D. A. Direct, rapid transfer of estrone from liposomes to microsomes. J Biol Chem. 1980 Jan 25;255(2):627–631. [PubMed] [Google Scholar]
  3. Buege J. A., Aust S. D. Microsomal lipid peroxidation. Methods Enzymol. 1978;52:302–310. doi: 10.1016/s0076-6879(78)52032-6. [DOI] [PubMed] [Google Scholar]
  4. FOLCH J., LEES M., SLOANE STANLEY G. H. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957 May;226(1):497–509. [PubMed] [Google Scholar]
  5. Friedberg T., Bentley P., Stasiecki P., Glatt H. R., Raphael D., Oesch F. The identification, solubilization, and characterization of microsome-associated glutathione S-transferases. J Biol Chem. 1979 Dec 10;254(23):12028–12033. [PubMed] [Google Scholar]
  6. Gibson D. D., Hornbrook K. R., McCay P. B. Glutathione-dependent inhibition of lipid peroxidation by a soluble, heat-labile factor in animal tissues. Biochim Biophys Acta. 1980 Dec 5;620(3):572–582. doi: 10.1016/0005-2760(80)90149-6. [DOI] [PubMed] [Google Scholar]
  7. Habig W. H., Pabst M. J., Jakoby W. B. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem. 1974 Nov 25;249(22):7130–7139. [PubMed] [Google Scholar]
  8. Holloway P. W. A simple procedure for removal of Triton X-100 from protein samples. Anal Biochem. 1973 May;53(1):304–308. doi: 10.1016/0003-2697(73)90436-3. [DOI] [PubMed] [Google Scholar]
  9. Jakoby W. B. The glutathione S-transferases: a group of multifunctional detoxification proteins. Adv Enzymol Relat Areas Mol Biol. 1978;46:383–414. doi: 10.1002/9780470122914.ch6. [DOI] [PubMed] [Google Scholar]
  10. Morgenstern R., DePierre J. W., Ernster L. Activation of microsomal glutathione S-transferase activity by sulfhydryl reagents. Biochem Biophys Res Commun. 1979 Apr 13;87(3):657–663. doi: 10.1016/0006-291x(79)92009-6. [DOI] [PubMed] [Google Scholar]
  11. Morgenstern R., Meijer J., Depierre J. W., Ernster L. Characterization of rat-liver microsomal glutathione S-transferase activity. Eur J Biochem. 1980 Feb;104(1):167–174. doi: 10.1111/j.1432-1033.1980.tb04412.x. [DOI] [PubMed] [Google Scholar]
  12. Szoka F., Jr, Papahadjopoulos D. Comparative properties and methods of preparation of lipid vesicles (liposomes). Annu Rev Biophys Bioeng. 1980;9:467–508. doi: 10.1146/annurev.bb.09.060180.002343. [DOI] [PubMed] [Google Scholar]
  13. Vessey D. A., Zakim D. Inhibition of glutathione S-transferase by bile acids. Biochem J. 1981 Aug 1;197(2):321–325. doi: 10.1042/bj1970321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Wirtz K. W., Devaux P. F., Bienvenue A. Phosphatidylcholine exchange protein catalyzes the net transfer of phosphatidylcholine to model membranes. Biochemistry. 1980 Jul 8;19(14):3395–3399. doi: 10.1021/bi00555a046. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES