title: Fluoride and beryllium interact with the (Na + K)-dependent ATPase as analogs of phosphate.
abstract: Fluoride irreversibly inhibits the (Na + K)-ATPase, and this inactivation requires divalent cations (Mg2+, Mn2+, or Ca2+), is augmented by K+, but is diminished by Na+ and by ATP. Prior incubation with the aluminum chelator deferoxamine markedly slows inactivation, whereas adding 1 microM AlCl3 speeds it, consistent with AlF-4 being the active species. Prior incubation of the enzyme with vanadate also blocks inactivation by fluoride added subsequently. Fluoride stimulates ouabain binding to the enzyme, and thus the analogy between AlF-4 and both orthophosphate and orthovanadate is reflected not only in the similar dependence on specific ligands for their enzyme interactions and their apparent competition for the same sites, but also in their common ability to promote ouabain binding. Beryllium also irreversibly inhibits the enzyme, and this inactivation again requires divalent cations, is augmented by K+, but is diminished by Na+ and by ATP. Similarly, prior incubation of the enzyme with vanadate blocks inactivation by beryllium added subsequently. Inactivation by beryllium, however, does not require a halide, and, unlike inactivation by fluoride, increases at basic pHs. These observations suggest that beryllium, as beryllium hydroxide complexes, acts as a phosphate analog, similar to AlF-4 and vanadate.
mesh_terms: D000535:Aluminum / Q000494:pharmacology; D017607:Aluminum Compounds; D000818:Animals; D001608:Beryllium / Q000494:pharmacology*; D001665:Binding Sites; D004285:Dogs; D005459:Fluorides / Q000494:pharmacology*; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D010042:Ouabain / Q000378:metabolism; D010710:Phosphates / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D017607:Aluminum Compounds; D010710:Phosphates; D010042:Ouabain; D000535:Aluminum; D000254:Sodium-Potassium-Exchanging ATPase; D001608:Beryllium; D005459:Fluorides; C032311:aluminum fluoride