1-Aminooxy-3-aminopropane, a new and potent inhibitor of polyamine biosynthesis that inhibits ornithine decarboxylase, adenosylmethionine decarboxylase and spermidine synthase.
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.
D012437:Adenosylmethionine Decarboxylase / Q000037:antagonists & inhibitors; D000818:Animals; D001921:Brain / Q000201:enzymology; D002417:Cattle; D006801:Humans; D007668:Kidney / Q000201:enzymology; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology; D051379:Mice; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000096:biosynthesis*; D011437:Propylamines / Q000494:pharmacology*; D011700:Putrescine / Q000494:pharmacology; D051381:Rats; D013095:Spermidine / Q000494:pharmacology; D011436:Spermidine Synthase / Q000037:antagonists & inhibitors
D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D011437:Propylamines; C046252:1-aminooxy-3-aminopropane; D011436:Spermidine Synthase; D012437:Adenosylmethionine Decarboxylase; D013095:Spermidine; D011700:Putrescine