ON THE NATURE OF THE INHIBITION OF GLUTAMATE OXIDATION BY THE CARCINOGEN, N-2-FLUORENYLDIACETAMIDE

Abstract

The inhibition of glutamate oxidation by various fluorene carcinogens was reported in a brief communication (1).Of the pyridine nucleotidelinked oxidations studied in rat liver mitochondria, n-glutamate, cy-ketoglutarate, cl-isocitrate, and m+hydroxybutyrate, only glutamate oxidation was markedly inhibited.The degree of this inhibition was roughly correlated with the known carcinogenicity of the fluorene compound (2).Further investigations on the nature of the inhibition are presented in this paper.'The results of these studies indicate that the carcinogen, N-2fluorenyldiacetamide,2 inhibits the glutamic dehydrogenase of mitochondria by acting as a powerful inhibitor of DPN+ for the enzyme.In this respect, the "native enzyme" present in mitochondria appears to be distinctly different from crystalline glutamic dehydrogenase, which is only slightly inhibited in a non-competitive manner by the carcinogen.Materials and Methods DPN+ and DPNH of 90 per cent purity, cytochrome c, and crystalline adenosine 5'-phosphate were commercial products.The fluorene compounds were generously contributed by Dr. H. P. Morris and Dr. H. Dyer; d-isocitrate was kindly supplied by Dr. G. H. Hogeboom.Crystalline glutamic dehydrogenase was a product of C. F. Boehringer,