Vanadate inhibits vacuolar H(+)-ATPase-mediated proton transport in chicken kidney microsomes by an ADP-dependent mechanism
| Autor: | William C. Home, Roland Baron, Pe’er David |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
ATPase
H+- vacuolar ATPase Biophysics Vacuole Kidney Biochemistry Acidification 03 medical and health sciences 0302 clinical medicine Adenosine Triphosphate Proton transport Microsomes Animals Nucleotide Vanadate Binding site Enzyme Inhibitors 030304 developmental biology chemistry.chemical_classification 0303 health sciences biology Chemistry Cell Biology Hydrogen-Ion Concentration Adenosine Diphosphate Kinetics Proton-Translocating ATPases Enzyme 030220 oncology & carcinogenesis Vacuoles biology.protein Microsome (Kidney) Vanadates Chickens Vacuolar H+-ATPase |
| Zdroj: | Biochimica et biophysica acta. 1280(1) |
| ISSN: | 0006-3002 |
| Popis: | Recent reports indicate that vacuolar-type proton ATPases from chicken osteoclasts (Chatterjee et al. (1992) Proc. Natl. Acad. Sci. USA 89, 6257–6261), yeast vacuoles and chromaffin granules (Beltran and Nelson (1992) Acta Physiol. Scand. Suppl. 607, 41–47) can be inhibited by vanadate, albeit at a concentration much higher than that required to inhibit P-type ATPases. We have characterized the mechanism by which vanadate inhibits vacuolar-type ATPase-mediated proton transport by chicken kidney microsomes. The initial rate of proton transport is somewhat less sensitive to vanadate than the total acidification, with IC50 values of 1.58 mM and 0.78 mM vanadate respectively. The inhibition of both the initial rate and total acidification is noncompetitive with respect to ATP. The inhibition is abolished when ADP is removed by an ATP-regenerating system, and the addition of exogenous ADP increases the vanadate inhibition of proton transport in a synergistic manner, thus demonstrating that inhibition by vanadate is dependent on the presence of ADP and explaining the lower effect of vanadate on the initial rate of acidification. Phosphate protects proton transport activity from inhibition by vanadate. These effects of ADP and phosphate suggest that inhibition by vanadate may involve the formation of a complex with ADP at a nucleotide binding site, possibly at the catalytic site of the enzyme. |
| Databáze: | OpenAIRE |
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