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Molecular Pharmacology

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Research ArticleArticle

Effects of Tranquilizers on the Glutamate Dehydrogenase- Glutamate-Oxalacetate Transaminase Complex

OTHMAN A. SHEMISA and LEONARD A. FAHIEN
Molecular Pharmacology November 1973, 9 (6) 726-735;
OTHMAN A. SHEMISA
Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706
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LEONARD A. FAHIEN
Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706
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Abstract

Perphenazine and haloperidol have been shown to be potent inhibitors of the reactions of keto or amino acids with glutamate dehydrogenase. These drugs do not significantly inhibit amino acid dehydrogenase reactions catalyzed by the complex formed between glutamate dehydrogenase and glutamate-oxalacetate transaminase, even though, in the presence of transaminase, they can still bind to glutamate dehydrogenase. Apparently, when these drugs are bound to glutamate dehydrogenase in the enzyme-enzyme complex, they cannot alter the conformation of this enzyme in the same manner that results in inhibition of the free enzyme. The transaminase-glutamate dehydrogenase complex catalyzes many amino acid dehydrogenase reactions with substrates such as tyrosine and aspartate. Since the enzyme-enzyme complex is not inhibited by these drugs, the amounts of transaminase and glutamate dehydrogenase in mitochondria are an important determinant of the degree of inhibition produced by these tranquilizers. If the levels of both enzymes are low, amino acid dehydrogenation would not be catalyzed by the complex, and perphenazine and haloperidol would be quite potent inhibitors. If the levels of both enzymes are high, the amino acid dehydrogenase reaction would be catalyzed mainly by the enzyme-enzyme complex, and these drugs would not be significant inhibitors.

  • Copyright ©, 1973, by Academic Press, Inc.

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Molecular Pharmacology
Vol. 9, Issue 6
1 Nov 1973
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Research ArticleArticle

Effects of Tranquilizers on the Glutamate Dehydrogenase- Glutamate-Oxalacetate Transaminase Complex

OTHMAN A. SHEMISA and LEONARD A. FAHIEN
Molecular Pharmacology November 1, 1973, 9 (6) 726-735;

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Research ArticleArticle

Effects of Tranquilizers on the Glutamate Dehydrogenase- Glutamate-Oxalacetate Transaminase Complex

OTHMAN A. SHEMISA and LEONARD A. FAHIEN
Molecular Pharmacology November 1, 1973, 9 (6) 726-735;
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