Ammonia excretion by the kidney has long been known to increase when a constant acid load is given to healthy subjects. This was clearly delineated by Sartorius, Roemmelt, and Pitts (1), who reported that when healthy humans were given a constant amount of ammonium chloride daily, there was a gradual increase in the excretion of ammonia, accompanied by an increased excretion of protons, and by an adaptation that resulted in the conservation of sodium and potassium ions.These experiments were preceded by those of Van Slyke and his co-workers (2), who had demonstrated that glutamine was extracted from the renal arterial blood of acidotic dogs in amounts sufficient to account for about 60% of the NH3 excreted by the kidneys-an observation recently confirmed and extended by the experiments of Pitts and his colleagues (3, 4). The infusion of a variety of amino acids into the acidotic dog has also been shown to increase the rate of excretion of ammonia (54), L-glutamine, L-asparagine, Land D-alanine, and L-histidine being the most effective.The nature of the metabolic pathways involved and the enzymes responsible for catalyzing the relevant reactions are not yet clearly understood.
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