Glutamine Extraction Research Articles

RELATIONSHIP OF PNH3 OF TUBULAR CELLS TO RENAL PRODUCTION OF AMMONIA.

Renal excretion of ammonia, addition of ammonia to renal venous blood, and total renal production of ammonia were measured in acidotic dogs before and during the intravenous infusion of ammonium chloride at rates of 0.5 and 1.0 mmole/min. Infusion of ammonium chloride increased urinary excretion of ammonia, reversed the direction of diffusion of ammonia between tubular cells and blood, i.e., induced the extraction of ammonia from blood, and reduced cellular production of ammonia. Production of ammonia was an inverse function of pNH3 of tubular cells. The infusion of ammonium lactate-N15 into one renal artery increased total ammonia excretion but decreased production of ammonia-N14 from normal blood-borne precursors. The intravenous infusion of ammonium chloride reduced extraction of glutamine from renal blood, yet increased the concentration of free glutamine in renal cortical cells. Our data suggest that an increase in pNH3 of tubular cells results in competitive inhibition of the glutaminase-1 reaction. We further suggest that the pNH3 of tubular cells is one factor governing renal production of ammonia; i e., the higher the cellular pNH3, the lower is the renal production of ammonia.

Extraction of amino acids from and their addition to renal blood plasma

Twenty paired samples of arterial and renal venous plasma, collected simultaneously from dogs in ammonium chloride acidosis, were analyzed by column chromatography for 23 α-amino acids. Fifteen additional paired samples from dogs in acute metabolic alkalosis were similarly analyzed. In ammonium chloride acidosis, glutamine plus asparagine, glycine, citrulline, tryptophan, and proline are extracted from renal blood plasma. Alanine, serine, glutamic acid, cystine, and ornithine are added to renal venous plasma. The addition of glutamic and aspartic acids amounts only to 4% of the extraction of glutamine plus asparagine. It is, therefore, probable that both α-amino and amide nitrogens are removed from the parent amide molecules. In acute metabolic alkalosis, the extraction of glutamine plus asparagine is halved, on an average. The extraction of glycine and the addition of alanine and serine are essentially unchanged. Therefore, only the extraction of glutamine plus asparagine varies to a quantitatively significant degree with changes in acid-base balance which markedly alter the rate of excretion of ammonia.