Twenty questions concerning the reaction cycle of the sarcoplasmic reticulum calcium pump

The problem of "mechanism" for the calcium pump may be divided into three parts. (1) It is an enzyme catalyzing the hydrolysis of ATP. (2) At some stage of the reaction cycle it provides a pathway through the otherwise impermeable phospholipid bilayer. (3) The two properties are linked so as to provide exchange of free energy between the two substrates (ATP and Ca2+), without any exchange of matter. The third part is the most interesting, and the mechanistic problem it poses is common to all chemiosmotic free energy transducers. All three aspects of the mechanism are reviewed here, with special emphasis on the remaining experimental questions that need to be resolved. The review will show that even such fundamental questions as the exact stoichiometry of the catalyzed reaction have not yet received definitive answers.