FIG. 6.

Model of the mechanism of action of UreI and HP0244. UreI transports urea at acidic periplasmic pH (pH < 6.2) and increasing urease activity, forming H₂CO₃ and 2 NH₃. Carbonic acid is converted to CO₂ in the cytoplasm by β-carbonic anhydrase and enters the periplasm, where it is converted by α-carbonic anhydrase to HCO₃⁺, enabling maintenance of periplasmic pH at ∼6.1. NH₃ exits via the bilayer and UreI, and NH₄⁺ is formed from the H⁺ generated by α-carbonic anhydrase and from protons entering from the medium. The NH₄⁺ generated in the cytoplasm exits via UreI, or perhaps via NH₃ + H⁺ exit. Acidification of the cytoplasm activates HP0244, which in turn allows assembly of the apoenzyme UreA/UreB with the nickel insertion pairs, UreE/UreG and UreF/UreH, activating urease at the membrane, providing local generation of carbonic acid and ammonia.