Mechanism of inhibition of histidine decarboxylase by rhodanines

Abstract

The inhibition of rat gastric histidine decarboxylase in vitro by rhodanine and 26 of its 3- or 5-substituted derivatives has been investigated. Inhibitory activities of the 3-substituted derivatives of rhodanine ranged from i 50 values of 2 × 10 −6 M to 2 × 10 −4 M. Eight 5-substituted derivatives were relatively inactive, yielding i 50 values higher than 5 × 10 −4 M. Studies performed with 3- p- chlorobenzylrhodanine ( i 50 = 3 × 10 −6 M) on preparations of histidine decarboxylase holoenzyme and apoenzyme indicated that only the holoenzyme form of the decarboxylase is susceptible to inhibition on treatment with an excess of the inhibitor, and that this inhibition is irreversible. The results are consistent with a mechanism of inhibition that involves a condensation reaction between the 5-methylene carbon of the rhodanine ring and enzyme-bound pyridoxal phosphate.