Different biochemical modes of action of two irreversible H+,K(+)-ATPase inhibitors, omeprazole and E3810.

摘要: Omeprazole and E3810 were found to inhibit gastric H+,K(+)-ATPase following different biochemical mechanisms. Effects of the specific binding inhibitors on conformational state enzyme studied by measuring fluorescence labeled with fluorescein 5'-isothiocyanate. The absolute level omeprazole-bound was lower than that control enzyme, reduction S-S cross-linking between omeprazole increased fluorescence. Addition K+ into vesicle solution quenched (E1-->E2K+). quench inhibited in but not E3810-bound enzyme. These results suggest has a low conformation (E2 form). On other hand, same as (E1 Phosphoenzyme formation absence both E3810- enzymes. Binding 2',3'-o-(2,4,6-trinitrophenyl)adenosine 5'-triphosphate equally omeprazole. K(+)-dependent dephosphorylation from phosphoenzyme experimental have shown inhibition mechanism E3810; partial reaction most differently affected change E2 E1 form for luminal E3810.