Fig. 2.

Schematic diagrams illustrating ammonia (NH₃) production and transport in the kidney. a NH₃ production in the proximal tubular cells. After glutamine uptake via sodium (Na⁺)-coupled neutral amino acid transporter 3 (SNAT3), mitochondrial glutamine metabolism results in production of ammonium (NH₄⁺). NH₃ passively diffuses across apical membrane and hydrogen (H⁺) is transported via apical Na⁺/H⁺ exchanger 3 (NHE3) and H⁺-ATPase; NH₃ and H⁺ combine in the lumen to form NH₄⁺. b NH₃ transport in the thick ascending limb. Lumen-positive voltage drives passive paracellular transport of NH₄⁺ from the lumen into the blood. By substituting for potassium (K⁺), NH₄⁺ is also transported into the cell via the Na⁺/K⁺/2Cl^– transporter and the apical membrane K⁺ channel (ROMK). The basolateral Na⁺/bicarbonate (HCO₃^–) cotransporter (NBCn2) may play a role in maintaining cellular pH. NH₄⁺ crosses the basolateral membrane into the blood via NHE4

(Adapted with permission from Palmer 2014 [6])