Molecular Pharmacology, Vol 15, 108-114, Copyright © 1979 by the American Society for Pharmacology and Experimental Therapeutics

Inhibition of Human and Rat Hepatic Aminotransferase Activity with L-3,4-Dihydroxyphenylalanine by Inhibitors of Peripheral Aromatic Amino Acid Decarboxylase

¹ Department of Biochemistry, University of Auckland, Auckland, New Zealand

Dopa aminotransferase activity in homogenates of human or rat liver was inhibited in vitro by MK 486. With the enzyme from rat, inhibition was more marked when -ketoglutarate was used as the amino group acceptor rather than phenylpyruvate. In concentrations up to 30 µM, NSD 1055 but not Ro 4-4602 also inhibited Dopa aminotransferase. All three drugs inhibited aromatic amino acid decarboxylase more effectively than Dopa aminotransferase. The degree of inhibition of Dopa aminotransferase activity by MK 486 was not affected by the pH of the assay. The inhibition could be overcome by high concentrations of pyridoxal phosphate. In vivo, Ro 4-4602, but not MK 486 caused an increase in the hepatic levels of Dopa--ketoglutarate and tyrosine--ketoglutarate aminotransferase activities in male rats. These drugs had little effect on the corresponding activities in female rats and no significant increase in the aminotransferase activities occurred when phenylpyruvate was used as the amino group acceptor.

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ACKNOWLEDGMENT The technical assistance of Mr. G. W. Smith is gratefully acknowledged. This research was supported by a grant from the Auckland Medical Research Foundation.