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DL-alpha-(Difluoromethyl)arginine (RMI 71 897) is an irreversible inhibitor of both
the biosynthetic and biodegradative arginine decarboxylases of Escherichia coli and
of the biosynthetic arginine decarboxylases of Pseudomonas aeruginosa and Klebsiella
pneumoniae. The Ki is close to 800 muM for the biosynthetic decarboxylase of E. coli
and 140 muM for the biodegradative enzyme while the respective half-lives (t1/2) calculated
for an infinite concentration of inhibitor are 1.0 and 2.1 min. The inhibitor also
blocks the arginine decarboxylase activity of E. coli and Pseudomonas aeruginosa in
vivo, indicating that the compound is transported into the cell. DL-alpha-Methylarginine
(RMI 71 699) was found to be a competitive inhibitor of both arginine decarboxylases
from E. coli. These results suggest that it may be possible to use an arginine decarboxylase
inhibitor in conjunction with known inhibitors of ornithine decarboxylase to block
all putrescine biosynthesis in prokaryotic cells and thus to study the effects of
such inhibition in these organisms.