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Renal ammoniagenesis predominantly results from glutamine metabolism, which produces 2 NH<jats:sub>4<\/jats:sub><jats:sup>+<\/jats:sup>and 2 HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>for each glutamine metabolized. The proximal tubule is the primary site for ammoniagenesis, but there is evidence for ammoniagenesis by most renal epithelial cells. Ammonia produced in the kidney is either excreted into the urine or returned to the systemic circulation through the renal veins. Ammonia excreted in the urine promotes acid excretion; ammonia returned to the systemic circulation is metabolized in the liver in a HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>\u2010consuming process, resulting in no net benefit to acid\u2010base homeostasis. Highly regulated ammonia transport by renal epithelial cells determines the proportion of ammonia excreted in the urine versus returned to the systemic circulation. The traditional paradigm of ammonia transport involving passive NH<jats:sub>3<\/jats:sub>diffusion, protonation in the lumen and NH<jats:sub>4<\/jats:sub><jats:sup>+<\/jats:sup>trapping due to an inability to cross plasma membranes is being replaced by the recognition of limited plasma membrane NH<jats:sub>3<\/jats:sub>permeability in combination with the presence of specific NH<jats:sub>3<\/jats:sub>\u2010transporting and NH<jats:sub>4<\/jats:sub><jats:sup>+<\/jats:sup>\u2010transporting proteins in specific renal epithelial cells. Ammonia production and transport are regulated by a variety of factors, including extracellular pH and K<jats:sup>+<\/jats:sup>, and by several hormones, such as mineralocorticoids, glucocorticoids and angiotensin II. This coordinated process of regulated ammonia production and transport is critical for the effective maintenance of acid\u2010base homeostasis. \u00a9 2013 American Physiological Society.<jats:italic>Compr Physiol<\/jats:italic>3:201\u2010220, 2013.<\/jats:p>","DOI":"10.1002\/cphy.c120010","type":"other","created":{"date-parts":[[2012,12,10]],"date-time":"2012-12-10T17:35:06Z","timestamp":1355160906000},"page":"201-220","source":"Crossref","is-referenced-by-count":139,"title":["Renal Ammonia Metabolism and Transport"],"prefix":"10.1002","author":[{"given":"I. 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