In the previous sections, we focused on transport proteins that move molecules down their concentration gradients (facilitated transport). Here we focus our attention on the class of proteins—the ATP-powered pumps—that use the energy released by hydrolysis of the terminal phosphoanhydride bond of ATP to transport ions and various small molecules across membranes against their concentration gradients. All ATP-powered pumps are transmembrane proteins with one or more binding sites for ATP located on subunits or segments of the protein that face the cytosol. These proteins are ATPases, but they normally do not hydrolyze ATP into ADP and Pi unless ions or other molecules are simultaneously transported. Because of this tight coupling between ATP hydrolysis and transport, the energy stored in the phosphoanhydride bond is not dissipated as heat, but rather is used to move ions or other molecules uphill against an electrochemical gradient.