Ammonia transport in the proximal tubule. Ammonia is produced in the proximal tubule primarily from metabolism of glutamine, and occurs primarily in the mitochondria. The enzymatic details of ammoniagenesis are not shown. Three transport mechanisms appear to mediate preferential apical ammonia secretion. These include Na+/NH4+ exchange via NHE-3, parallel NH3 secretion and NHE-3-mediated Na+/H+ exchange, and a Ba2+-sensitive NH4+ conductance likely mediated by apical K+ channels. Secreted NH3 is titrated to NH4+ by reaction with H+, which is secreted either by NHE-3 or by apical H+-ATPase. HCO3− is produced in equimolar amounts as NH4+ in the process of ammoniagenesis, and is primarily transported across the basolateral plasma membrane by NBCe1. Minor components of basolateral NH4+ uptake via Na+-K+-ATPase and by basolateral K+ channels are not shown. Figure modified from reference (180) with permission.