Premium
THE INTERACTIONS OF CHOLINE MUSTARD AZIRIDINIUM ION WITH CHOLINE ACETYLTRANSFERASE (EC 2.3.1.6)
Author(s) -
Rylett B. Jane,
Colhoun E. Howard
Publication year - 1979
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1979.tb00383.x
Subject(s) - choline acetyltransferase , choline , acetylcholine , chemistry , nitrogen mustard , ion , substrate (aquarium) , biochemistry , acetylation , stereochemistry , organic chemistry , pharmacology , biology , ecology , genetics , chemotherapy , gene , cyclophosphamide
— The nitrogen mustard analogue of choline, choline mustard aziridinium ion, was studied as a substrate and inhibitor of choline acetyltransferase in crude homogenates of rat brain. The compound was acetylated at a maximum velocity (V max ) of 1.51±0.33μmol/g tissue/h with an apparent K m of 4.63± 0.17 mM. The V max for choline was 5.25±0.15μmol/g tissue/h with a K m of 1.70±0.17mM indicating that the affinity and rate of acetylation of choline mustard aziridinium ion was about 3 times less. Choline mustard aziridinium ion was a competitive inhibitor of choline acetyltransferase with a K i of 1.8 mM. The generation of aziridiniurn ion from acetylcholine mustard was determined at 25°C and the concentration of ion in aqueous solution was inversely related to the concentration or acetylcholine mustard; the optimum ion concentration of 70% was obtained at 10 mg acetylcholine mustard/ml solution. The ineffective generation of aziridiniurn ion at high concentrations of acetylcholine mustard placed limitations on the design and evaluation of the kinetic experiments with choline acetyltransferase. Nevertheless, the present experiments demonstrate that choline mustard aziridrnium ion interacts with choline acetyltransferase and they may provide evidence for a clearer understanding in the in vivo actions of certain nigrogen mustard analogues.