Pathways of ammonia metabolism in the intact functioning kidney of the dog

Abstract

Studies in which (15)N-labeled precursors of urinary ammonia were infused into the artery of an intact functioning kidney of an acidotic dog have led to the following conclusions: Preformed ammonia and ammonia derived from the amide nitrogen of plasma glutamine are added directly to urine without significant incorporation into amino acid intermediates of renal tissue. Thus, reductive amination of alpha-ketoglutarate to form glutamate does not occur to an appreciable extent nor is there significant transfer of the amide nitrogen of glutamine to the corresponding keto acids to form glutamate, aspartate, alanine, or glycine. The enzyme system "glutaminase II" may participate to a significant extent in the metabolism of glutamine by forming aspartate and alanine by direct transamination of oxalacetate and pyruvate and liberating the amide nitrogen as ammonia. Renal alanine exists as a well mixed pool derived in roughly equal amounts from filtered and reabsorbed plasma alanine and newly synthesized alanine. The alanine pool of tubular cells does not equilibrate with the alanine of peritubular capillary blood. Transfer of the nitrogen of alanine to alpha-ketoglutarate and subsequent oxidative demination of the resulting glutamate can account for the ammonia formed from alanine. Glycine is not an important intermediate in renal nitrogen metabolism.