ATP driven ion pumps: an evolutionary mosaic

Ion pumps driven by ATP are found in all species from bacteria to plants and animals. The early observation of functional relationships between these pumps has now been amply confirmed by their amino acid sequences. The evidence from electron microscopy that about two-thirds of the molecule projects into the cytoplasm and is phosphorylated by ATP has provided a framework for interpreting the reaction cycle. The phosphorylation is dependent on binding of the cation which is pumped out of the cell. For the Calf pump of sarcoplasmic reticulum, the translocation of 2 Ca'+ is coupled to loss of reactivity of the phosphoenzyme to ADP. This is followed by release of Ca2+ to the exterior, hydrolysis of the phosphoenzyme and release of phosphate in the cytoplasm. About 25 pumps have been sequenced during the past 4 years (Table I) . It can be seen that the ion pumped out of the cytoplasm can be H +, Na+, Ca? + or even Cd? +. whereas the counterion, if any, has so far always been K'. This may be the result of a biological requirement for high cytoplasmic K + rather than a requirement of the chemical mechanism. In most bacterial pumps and in plants, the ion which activates phosphorylation is the proton, though some less well-characterized bacterial pumps can handle metal cations [ 1,2]. The reaction cycles of the Na' and Ca2+ pumps have been studied in great detail [ 3 , 41 and the rate constants of most of the steps of the latter have been measured. The cycle is reversible, allowing ATP synthesis to be driven by an ion gradient. At its heart, is the phosphoenzyme intermediate,