Competitive inhibitors slow, tight-binding

Two special classes of competitive inhibitors are characterized by slow binding and slow, tight binding... 

Irreversible enzyme inhibition, also cahed enzyme inactivation (or active-site directed ineversible inhibition, because it is generally competitive with substrate), occurs when a compound blocks the enzyme activity for an extended period of time, generally via covalent bond formation. Therefore, even though some slow tight-binding inhibitors functionahy block the enzyme activity irreversibly, they are stih considered reversible... 

Sodium l,l-dimethoxyethyl(methyl)phosphinate 2 was found to be the most effective herbicidal compound among plant PDHc El inhibitors by Baillie et al. s work. 2 was presumably hydrolyzed to sodium salt of acetyl(methyl)phosphinic acid 1-2 in vivo to exhibit herbicidal activity (Scheme 4.10). 1-2 displayed higher enzyme inhibition and herbicidal activity than 1-1. It has been found that 1-1 was a competitive inhibitor of PDHc, but 1-2 caused time-dependent inhibition. Baillie et al. gave a possible explanation for this result, the initial binding of inhibitors to the pyruvate site and subsequent reaction with thiamine pyrophosphate were rapid and reversible for both 1-1 and 1-2. In the case of 1-2, an enzyme-inhibitor complex was first formed and then underwent a time-dependent, essentially irreversible transformation to produce a more tightly bound form. In other words, 1-2 could act as a slow, tight binding inhibitor [1]. 

Specific small molecules or ions can inhibit even nonallosteric enzymes. In irreversible inhibition, the inhibitor is covalently linked to the enzyme or bound so tightly that its dissociation from the enzyme is very slow. Covalent inhibitors provide a means of mapping the enzyme s active site. In contrast, reversible inhibition is characterized by a rapid equilibrium between enzyme and inhibitor. A competitive inhibitor prevents the substrate from binding to the active site. It reduces the reaction velocity by diminishing the proportion of enzyme molecules that are bound to substrate. In noncompetitive inhibition, the inhibitor decreases the turnover number. Competitive inhibition can be distinguished from noncompetitive inhibition by determining whether the inhibition can be overcome by raising the substrate concentration. 

In a recent report, by making a slight modification in the structure of the parent compound, two additional compounds with slightly higher activity have been synthesized (36). TFT and the aliphatic trifluoromethyl ketones appeared to be classical competitive inhibitors, while many trifluoropropanone sulfides were found to be reversible but slow and tight binding inhibitors of JHE... 

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