Blocking of Pentose Phosphate Pathway in the Brain of Rats by 6-Aminonicotinamide

  • H. Herken
  • K. Lange


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).


Pentose Phosphate Pathway 6-Aminonicotinamide 6-Phos-pho D-Gluconate: NADP Oxidoreductase 6-Phosphogluconate. 


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  1. Bruchhausen, F. v., u. H. Herken: Wirkung des 6-Aminonikotinsäureamids auf die insulinabhängige Glucoseaufnahme in das epidymale Fettgewebe. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 254, 388 (1966).CrossRefGoogle Scholar
  2. 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
  3. —: u. H. Herken: Biosynthese von 3-Acetylpyridin-adenin-dmucleotidphosphat (3-APADP) aus Nicotinamidadenin-dinucleotidphosphat (NADP). Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 245, 541 (1963).CrossRefGoogle Scholar
  4. Coper, H., H. Hadass u. H. Lison: Untersuchungen zum Mechanismus zentralnervöser Funktionsstörungen durch 6-Aminonicotinamid. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 255, 97 (1966).CrossRefGoogle Scholar
  5. —, u. H. Herken: Schädigung des Zentralnervensystems durch Antimetaboliten des Nikotinsäureamids. Dtsch. med. Wschr. 88, 2025 (1963).PubMedCrossRefGoogle Scholar
  6. —, u. D. Neubert: Einfluß von NADP-Analogen auf die Reaktionsgeschwindigkeit einiger NADP-bedürftiger Oxydoreduktasen. Biochim. biophys. Acta (Amst.) 89, 23 (1964).Google Scholar
  7. Dietrich, L.S., I.M. Friedland, and L.A. Kaplan: Pyridine nucleotide metabolism: Mechanism of action of the niacin antagonist 6-amino-nicotinamide. J. biol. Chem. 233, 964 (1958).PubMedGoogle Scholar
  8. Herken, H.: Drug-induced pathobiotic effects. In: Proc. 3rd. Intern. Pharmacological Meeting, Vol. 4, p. 3, Mechanisms of drug toxicity. Oxford-New York: Pergamon Press 1968 a.CrossRefGoogle Scholar
  9. —: Biosynthesis and action of dinucleotides containing 6-aminonicotinamide on membrane transport processes. Arzneimittel-Forsch. 18, 1235 (1968b).Google Scholar
  10. —, u. V. Neuhoff: Spektrofluorometrische Bestimmung des Einbaus von 6-Aminonicotinsäureamid in die oxydierten Pyridinnucleotide der Niere. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 247, 187 (1964).CrossRefGoogle Scholar
  11. 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
  12. Johnson, W.J., and J.D. McColl: Antimetabolic activity of 6-aminonicotinamide. Fed. Proc. 15, 284 (1965).Google Scholar
  13. Noltmann, E., u. F.H. Bruns: Reindarstellung und Eigenschaften von Phosphoglucose-isomerase aus Hefe. Biochem. Z. 331, 436 (1959).Google Scholar
  14. Parr, C.W.: Inhibition of phosphoglucose isomerase. Nature (Lond.) 178, 1401 (1956).CrossRefGoogle Scholar
  15. —: Competitive inhibitors of phosphoglucose isomerase. Biochem. J. 65, 34 P (1957).Google Scholar
  16. Racker, E.: Mechanisms in bioenergetics, p. 207. New York-London: Academic Press 1965.Google Scholar
  17. Salas, M., E. Vinuela, and A. Sols: Spontaneous and enzymatically catalyzed anomerization of glucose 6-phosphate and anomeric specificity of related enzymes. J. biol. Chem. 240, 561 (1965).PubMedGoogle Scholar
  18. 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

Copyright information

© Springer-Verlag Berlin Heidelberg 1969

Authors and Affiliations

  • H. Herken
    • 1
  • K. Lange
    • 1
  1. 1.Pharmakologisches InstitutFreien UniversitätBerlin 33Deutschland

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