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gated by the substitution of this analog for DPN or triphosphopyridine nucleotide (TPN) in the specific assay systems for the following pyridine nucleotiderequiring oxidative enzymes7: alcohol dehydrogenase (DPN), a-keto-glutaric dehydrogenase (DPN), malic dehydrogenase (DPN), P-hydroxy-acyl Co-1 dehydrogenase (DPN), isocitric dehydrogenase (TPN) and malic enzyme (TPN). D-INAH-N is not reduced in these reactions. Furthermore, the reduction by their specific dehydrogenases of either D P N or T P N is not inhibited by D-INAH-N. The oxidation of D P N H by the specific DPN-cytochrome c reductase7 of pig heart muscle is not inhibited by D-INAH-N. These several pyridine nucleotide-requiring dehydrogenases were tested in order to obtain as broad a picture as possible of the potential inhibiting nature of this analog. This anomalous behavior may be interpreted as evidence that DPN is normally reduced by the addition of a proton to the 4-position of the pyridine ring; this position is apparently unavailable in DI N X H - S where the pyridine ring is substituted in the para position. ?'his confirms the recent report who investigated the stereospecby Pullman, et d.,* ificity of DPN reduction. These workers concluded from isotope experiinents that D P N was reduced in the para position of the pyridine ring. The antituberculous action of INAH may accordingly be due to the intracellular formation of an inactive pyridine nucleotide analog with a concomitant reduction in cellular oxidative metabolism. ( 7 ) Generously supplied b y Drs. H. R. Mahler, D. R. Sanadi a n d S. \Vakil, Enzyme Institute, University of Wisconsin. ( 8 ) AI. E. Pullman, A. S a n Pietro a n d S. P. Colowick, J . Diol. C h i n . , 206, 129 (1954). RESEARCH DIVISION \'ETERANS :\UhZINISTRATION
HOSPITAL DEXTER s. GOLDMAN
AIADISOX,WISCONSIN RECEIVED FEBRUARY 3 , 195-i
URIDINE-A N D INOSINE-TRIPHOSPHATESAS PHOSPHATE DONORS FOR PHOSPHOHEXOKINASEL
Si?. 'The widespread natural occurrence of the 5 'tripliosp1i:ites of uridine2-6 (UTP), inosinea (ITP) aiid other nucleosides raises the question of whether they participate directly in phosphorylating react i o n ~ ~in . ' addition to their possible role in nucleic acid synthesis. Kleinzeller8 reported ITP to be inactive in the phosphorylation of fructose-&phosphate with muscle extract as the enzyme source, but Muntzg reported this nucleotide to be half as active as *ITPwhen a partially purified phosphofructokinase j I ! Supgorted in p a r t b y a grant-in-aid f r o m t h e American Cancer S i r i r t v upon recommendation of t h e Committee o n Growth of t h e N u t i o n a l Research Council. ( 2 ) S. A. K u b y , M.S. Thesis, University of Wisconsin, Madison ~l't.xl~.
re! .I Kornberg, Phosphorur Metabolism, 1, 392 (1961). S. A. Morell, A. Friedeo a n d R. A I . Bock, THIS 5-119 (1953). Eergkvist a n d A. Deutsch, Acta Chem. Scand., 7 , 1307
[ I ! S . 1%.Lipton, JG!IK X ~ I 7 , 6,
li ( 1g.ix
ili) €I. Schmitz,
V. R. Potter, R. B. Hurlbert a n d D. White, Cancer
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