L. S. Dietrich, I. Friedland, L. Kaplan
Oct 1, 1958
Citations
3
Influential Citations
137
Citations
Quality indicators
Journal
The Journal of biological chemistry
Abstract
6-Aminonicotinamide has been reported to be a powerful niacin antagonist (1) and effective against certain experimental neoplasms (2-4). A compound tentatively identified as the g-AN1 analogue of DPN has been isolated from tissues of 6-ANtreated animals and synthesized enzymatically employing pig brain DPNase (2). Our interest in antimetabolites of vitamins and their mechanism of action led us to explore the metabolic action of this new compound. We have isolated from B-AN-treated mice the 6-AN analogue of DPN and TPN and have synthesized these compounds in vitro. These nucleotide analogues, contrary to the report of Johnson et al. (2), undergo none of the addition reactions which occur with normal pyridine nucleotides, i.e. hydrosulfite reduction or cyanide, acetone, and dihydroxyacetone addition. Administration of 6-AN to mice causes a marked reduction in the activity of DPN-dependent mitochondrial systems, /3hydroxybutyrate and a-ketoglutarate dehydrogenase. In the 755 adenocarcinoma, where a relatively low enzymatic capacity to carry out oxidative phosphorylation is coupled with a high energy requirement, (indicated by the very rapid growth of the tumor), marked lowering of the ATP and ADP, and increases in the AMP concentration were observed upon the administration of 6-AN.