Studies of endogenous inhibitors of microsomal glutathione S-transferase.

Thomas D Boyer, D. Zakim, D. A. Vessey

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)57-64
Number of pages8
JournalBiochemical Journal
Volume207
Issue number1
StatePublished - Oct 1 1982
Externally publishedYes

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Glutathione Transferase
Unilamellar Liposomes
Phosphatidylcholines
Lysophosphatidylcholines
Palmitates
Poisons
Liver
Enzyme Inhibitors
Enzymes
Transferases
Nonesterified Fatty Acids
Metabolism
Rats
Hepatocytes
Membranes
Therapeutics

ASJC Scopus subject areas

  • Biochemistry

Cite this

Studies of endogenous inhibitors of microsomal glutathione S-transferase. / Boyer, Thomas D; Zakim, D.; Vessey, D. A.

In: Biochemical Journal, Vol. 207, No. 1, 01.10.1982, p. 57-64.

Research output: Contribution to journalArticle

Boyer, Thomas D ; Zakim, D. ; Vessey, D. A. / Studies of endogenous inhibitors of microsomal glutathione S-transferase. In: Biochemical Journal. 1982 ; Vol. 207, No. 1. pp. 57-64.
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