FIGURE 7.

Ammonia transport mechanisms in the proximal tubule. Glutamine serves as the primary metabolic substrate for ammoniagenesis. Proximal tubule glutamine uptake (influx) involves transport across the apical plasma membrane, primarily via the broad specificity, Na⁺-dependent amino acid cotransporter B^OAT-1 (SLC6A19), and across the basolateral plasma membrane by the Na⁺-coupled neutral amino acid transporter SN1 (SLC38A3). Complete metabolism of each glutamine results in mitochondrial generation of two NH₄⁺ and two HCO₃⁻. At least a component of mitochondrial ammonia appears to be transported from mitochondria to the cytosol via AQP8. Although shown as NH₄⁺ transport, whether this occurs as NH₄⁺ transport or as AQP8-mediated NH₃ transport with H⁺ transport through an alternative mechanism has not been examined. Bicarbonate is transported across the basolateral plasma membrane via the electrogenic sodium bicarbonate cotransporter, isoform 1A, NBCe-1A (SLC4A4). Ammonium secretion across the apical plasma membrane occurs primarily via NHE3-mediated Na⁺/NH₄⁺exchange, with a lesser contribution by parallel H⁺ and NH₃ transport. The mechanism enabling NH₃ transport, whether diffusive transport across the apical plasma membrane or via a specific transporter, has not been identified.