Inhibition of the ketohexokinase from liver by benzothiadiazines

Abstract

The action 011 the ketohexokinase (ATP : D-fructose 1 phos- photransferase) of three diuretic benzothiadiazines is studied : Hydroflumethiazide (HFM), Hydrochlorothiazide (HCT) and Chlorothiazide (CT)”ž The inhibition produced by HFM is im- portant (70 % at 5 x 10-4 M conc.) though inferior to that exercised by the HS-groups reagents ; and it is not reversible by an excess of cj^steine. The inhibitory effectiveness series of three benzothiadiazines (Table I) is HFM>HCT>CT. There is no parallelism between the inhibitions produced by these drugs on the carbonic anhydrase and upon the ketohexokinase. Neither, may a direct relation to their natriuretic activity be established.