Does urea synthesis play a role in bicarbonate disposal?

It has traditionally been assumed that the urea cycle serves primarily to dispose of potentially toxic ammonia resulting from the catabolism of endogenous and dietary protein. Bicarbonate is also a substrate for the first enzymatic step of the urea cycle, catalysed by CPS. In recent years, it has been suggested that during the complete oxidation of dipolar amino acids, a proton is consumed from the body buffer, resulting in the stoichiomeuic generation of bicarbonate anion along with ammonia [l-41. An alternative scheme has therefore been proposed in which ureagenesis serves equally in the disposal of metabolic bicarbonate as well as ammonia, resulting from the catabolism of ingested protein. The aim of this study was to directly test the above hypothesis by examining the rate of urea excretion under conditions of limiting dietary amino acid provision. Three groups of rats were fed either a standard protein (17%) diet, a PF2 diet, or a PF diet with simultaneous access to a 0.28M solution of NH4Q for 10 days. Daily urine samples were collected under mineral oil. Prior to sacrifice on the tenth day, aerobic and anaerobic blood samples were taken from the rats for measurement of blood pH, blood bicarbonate, and serum urea levels. Both groups of rats ingesting PF diet exhibited profound metabolic acidosis (Table 1). Serum urea levels were also significantly decreased in both these groups; however in rats simultaneously ingesting NH4C1, serum urea levels were significantly greater than in rats consuming PF diet only (Table 1; p < 0.05). Urinary urea excretion was also significantly increased on all days examined in rats supplemented with ammonium relative to those consuming PF diet only (Fig. 1) . The increase in urea excretion in the ammonium supplemented group occurred in spite of the reduction in extracellular [HC03-] relative to standard protein fed controls. These results suggest therefore that exogenous ammonium can be metabolised via the urea cycle without the simultaneous provision of exogenous bicarbonate substrate, i.e. in the absence of bicarbonate generated from the catabolism of dietary amino acids. These findings are in general agreement with those of other workers [5-81 and suggest that ureagenesis serves primarily to dispose of ammonia rather than bicarbonate during normal acid-base homeostasis.