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1-Aminooxy-3-aminopropane, a new and potent inhibitor of polyamine biosynthesis that inhibits ornithine decarboxylase, adenosylmethionine decarboxylase and spermidine synthase.

Abstract
1-Aminooxy-3-aminopropane was shown to be a potent competitive inhibitor (Ki = 3.2 nM) of homogenous mouse kidney ornithine decarboxylase, a potent irreversible inhibitor (Ki = 50 microM) of homogeneous liver adenosylmethionine decarboxylase and a potent competitive (Ki = 2.3 microM) of homogeneous bovine brain spermidine synthase. It did not inhibit homogeneous bovine brain spermine synthase and it did not serve as a substrate for spermidine synthase. The compound did not inhibit tyrosine aminotransferase, alanine aminotransferase or aspartate aminotransferase, which are pyridoxal phosphate-containing enzymes like ornithine decarboxylase. The inactivation of adenosylmethionine decarboxylase was partially prevented by pyruvate, which is the coenzyme of adenosylmethionine decarboxylase, and by the substrate, adenosylmethionine. 1-Aminooxy-3-aminopropane at 0.5 mM concentration inhibited the growth of HL-60 promyelocytic leukemia cells and this inhibition was prevented by spermidine but not by putrescine.
AuthorsR M Khomutov, T Hyvönen, E Karvonen, L Kauppinen, T Paalanen, L Paulin, T Eloranta, R L Pajula, L C Andersson, H Pösö
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 130 Issue 2 Pg. 596-602 (Jul 31 1985) ISSN: 0006-291X [Print] United States
PMID3861182 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Ornithine Decarboxylase Inhibitors
  • Polyamines
  • Propylamines
  • 1-aminooxy-3-aminopropane
  • Spermidine Synthase
  • Adenosylmethionine Decarboxylase
  • Spermidine
  • Putrescine
Topics
  • Adenosylmethionine Decarboxylase (antagonists & inhibitors)
  • Animals
  • Brain (enzymology)
  • Cattle
  • Humans
  • Kidney (enzymology)
  • Leukemia, Myeloid, Acute (enzymology)
  • Mice
  • Ornithine Decarboxylase Inhibitors
  • Polyamines (biosynthesis)
  • Propylamines (pharmacology)
  • Putrescine (pharmacology)
  • Rats
  • Spermidine (pharmacology)
  • Spermidine Synthase (antagonists & inhibitors)

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