Organization of hepatic nitrogen metabolism and its relation to acid-base homeostasis

Hepatic and renal nitrogen metabolism are linked by an interorgan glutamine flux, coupling both renal ammoniagenesis and hepatic ureogenesis to systemic acid base regulation. This is because protein breakdown produces equimolar amounts of NH4+ and HCO3-. A hepatic role in this interorgan team effort is based upon the tissue-specific presence of urea synthesis, which represents a major irreversible pathway for removal of metabolically generated bicarbonate. A sensitive and complex control of bicarbonate disposal via ureogenesis by the extracellular acid-base status creates a feed-back control loop between the acid-base status and the rate of bicarbonate elimination. This bicarbonate-homeostatic mechanism operates without threat of hyperammonemia, because a sophisticated structural and functional organisation of ammonia-metabolizing pathways in the liver acinus uncouples urea synthesis from the vital need to eliminate potentially toxic ammonia.