Physiology of V-ATPases

Abstract

Protons migrate much faster than other ions through water, ice and water-lined membrane channels because they participate in hydrogen bonding and H+H2O exchange. Similarly, hydrogen bonding enables protons with amino, carbonyl, phosphoryl and sulfonyl residues to influence critically the charge, conformation and stability of proteins. Therefore, it is not surprising that regulation of proton concentration, or pH, is an essential requirement in biological systems. It is no surprise either that enzymes which regulate proton concentration (i.e. proton pumps) should have evolved or that evolution should have used these enzymes further, for energization of biological membranes. At present there appear to be three classes of ATP-hydrolyzing proton pumps, or H+-ATPases, which were dubbed P-ATPases, F-ATPases and V-ATPases, by Pederson and Carafoli (1987). H+-translocating P-ATPases, as well as the Na+/K+-ATPase of plasma membranes and the Ca2+-ATPase of sarcoplasmic reticulum, form phosphoaspartyl intermediates and are inhibited by the phosphate analogue orthovanadate. F-ATPases are the proton-translocating ATP synthases of mitochondria, chloroplasts and bacterial plasma membranes and are inhibited by azide.