Blocking of Pentose Phosphate Pathway in the Brain of Rats by 6-Aminonicotinamide
The biosynthesis of derivatives of NAD and NADP containing 6-aminonicotinamide (6-AN) entails functional disorders in different Organs, amongst which central nervous disorders are most conspicuous (Johnson and McColl,1956; Wolf Cowen, nd Geller,1959). A continuous drop in body temperature and a prolongation of sleepjng time after application of hexobarbital which is not due to a delayed turnover of the drug, are found besides progressive paralysis (Coper and Herken,1963: Coper Hadass, and Lison, 1966; Herken, 1968a). Spectrofluorometric studies showed that the enzymic conversion of nicotinamide to 6-aminonicotinamide was particularly high in the NADP-fraction (Herken and Neuhoff, 1964; Herken, 1968b). This is important because, in the brain, KADP is present in much lower concentrations than NAD, and because the conversion of NADP to 6-AXADP will considerably change the function of the enzymes needing NADP. It was also possible to establish on isolated microsomes that the synthesis of abnormally structured nucleotides by the glycohydrolase after addition of antimetabolites of nicotinamide is faster in the presence of NADP than it is if NAD is used (Brunneman Coper, and Herken, 1963). These abnormally structured nucleotides are unable to act as hydrogen carriers in oxidoreductase systems (Dietrich Friedland, and Kaplan, 1958).
Key-WordsPentose Phosphate Pathway 6-Aminonicotinamide 6-Phos-pho D-Gluconate: NADP Oxidoreductase 6-Phosphogluconate.
Unable to display preview. Download preview PDF.
- Brunnemann, A., u. H. Coper: Die Aktivität NAD-und NADP-abhängiger Enzyme in verschiedenen Teilen des Rattengehirns. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 246, 493 (1964).Google Scholar
- —, u. D. Neubert: Einfluß von NADP-Analogen auf die Reaktionsgeschwindigkeit einiger NADP-bedürftiger Oxydoreduktasen. Biochim. biophys. Acta (Amst.) 89, 23 (1964).Google Scholar
- —: Biosynthesis and action of dinucleotides containing 6-aminonicotinamide on membrane transport processes. Arzneimittel-Forsch. 18, 1235 (1968b).Google Scholar
- Horecker, B.L.: Pentose phosphate pathway, uronic acid pathway, interconversion of sugars. In: Carbohydrate metabolism and its disorders, Vol. I, p. 139. London-New York: Academic Press (1968).Google Scholar
- Johnson, W.J., and J.D. McColl: Antimetabolic activity of 6-aminonicotinamide. Fed. Proc. 15, 284 (1965).Google Scholar
- Noltmann, E., u. F.H. Bruns: Reindarstellung und Eigenschaften von Phosphoglucose-isomerase aus Hefe. Biochem. Z. 331, 436 (1959).Google Scholar
- —: Competitive inhibitors of phosphoglucose isomerase. Biochem. J. 65, 34 P (1957).Google Scholar
- Racker, E.: Mechanisms in bioenergetics, p. 207. New York-London: Academic Press 1965.Google Scholar
- Wolf, A., D. Cowen, and L.M. Geller: The effects of an antimetabolite, 6-aminonicotinamide, on the central nervous system. Transact. Amer. neurol. Ass. 1959, 140.Google Scholar