ISSN:
1434-193X
Keywords:
Bioorganic chemistry
;
Enzyme inhibitors
;
Aldolase
;
Structure-activity relationship
;
Enzyme mechanism
;
Chemistry
;
General Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
The mechanistic reaction pathway for the slow-binding inhibition of rabbit muscle aldolase by D-glycero-tetrulose 1-phosphate (D-erythrulose 1-phosphate) was investigated through the use of its phosphonomethyl isoster 4 which was synthezised for this study. The latter is not a substrate nor a slow-binding inhibitor but interferes in the enzyme-catalyzed reaction with the substrate fructose 1,6-diphosphate in a competitive manner. It was found that phosphonate 4 forms an iminium ion with aldolase and undergoes subsequent α-proton abstraction to form an enamine intermediate. We show from these results that enzyme slow-binding inhibition by D-erythrulose 1-phosphate is consistent with a phosphate β-elimination reaction through the enamine intermediate. This mechanism takes into account the stereochemical features known for aldolase, the parallel between enzyme activity recovery and phosphate release after action of D-erythrulose 1-phosphate, and also the same reaction from dihydroxyacetone phosphate.
Type of Medium:
Electronic Resource
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