title: Is urea formation regulated primarily by acid-base balance in vivo?
abstract: Large quantities of ammonium and bicarbonate are produced each day from the metabolism of dietary protein. It has recently been proposed that urea synthesis is regulated by the need to remove this large load of bicarbonate. The purpose of these experiments was to test whether the primary function of ureagenesis in vivo is to remove ammonium or bicarbonate. The first series of rats were given a constant acid load as hydrochloric acid or ammonium chloride; individual rats received a constant nitrogen load at a time when their plasma acid-base status ranged from normal (pH 7.4, 28 mM HCO3) to severe metabolic acidosis (pH 6.9, 6 mM HCO3). Urea plus ammonium excretions and the blood urea, glutamine, and ammonium concentrations were monitored with time. Within the constraints of non-steady-state conditions, the rate of urea synthesis was constant and the plasma glutamine and ammonium concentrations also remained constant; thus it appears that the rate of urea synthesis was not primarily regulated by the acid-base status of the animal in vivo over a wide range of plasma ammonium concentrations. In quantitative terms, the vast bulk of the ammonium load was converted to urea over 80 min; only a small quantity of ammonium appeared as circulating glutamine or urinary ammonium. Urea synthesis was proportional to the nitrogen load. A second series of rats received sodium bicarbonate; urea synthesis was not augmented by a bicarbonate load. We conclude from these studies that the need to dispose of excess bicarbonate does not primarily determine the rate of ureagenesis in vivo. The data support the classical view that ureagenesis is controlled by the quantity of ammonium to be removed.
authors.forename: M L
authors.initials: ML
authors.lastname: Halperin
authors.forename: C B
authors.initials: CB
authors.lastname: Chen
authors.forename: S
authors.initials: S
authors.lastname: Cheema-Dhadli
authors.forename: M L
authors.initials: ML
authors.lastname: West
authors.forename: R L
authors.initials: RL
authors.lastname: Jungas
mesh_terms: D000136:Acid-Base Equilibrium; D000138:Acidosis / Q000378:metabolism; D000641:Ammonia / Q000097:blood; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D002245:Carbon Dioxide / Q000378:metabolism; D005973:Glutamine / Q000097:blood; D008297:Male; D009584:Nitrogen / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D014508:Urea / Q000096:biosynthesis* / Q000097:blood
chemical_list: D001639:Bicarbonates; D011506:Proteins; D005973:Glutamine; D002245:Carbon Dioxide; D000641:Ammonia; D014508:Urea; D009584:Nitrogen