A Relation Between α-Ketoglutarate Utilization and Excretion of Ammonia, Titratable Acid, Sodium Reabsorption and Renal Gluconeogenesis in Man

Abstract

In vivo utilization of the renotropic substrate alphaketoglutarate (α-Kg) is associated with a high RQ and augments the glutamate pool. The glutamate pool influences glutaminase-I activity and NH₄ production. In vitro studies show that α-Kg may contribute to titratable acid (TA) formation, and to reneal gluconeogenesis (RGP). RGP has been coupled with ammoniagenesis. The present studies in man demonstrate that these several processes may be interelated through metabolism of α-Kg. Trans-renal extractions of α-Kg, glucose, oxygen and PAH with measurementz of inulin and PAH clearances, Na, NH₄ + and TA excretions were measured in 6 children with acyanotic congenital heart defects and 4 children with normal renal functions, recovering from glomerulonephritis, during an infusion of Na α-Kg. The urinary pH rose from 5.2 to 6.1. α-Kg infusion increased RGP, fract ional Na reabsorption (R_Na), and TA, but decreased NH₄ + excretion. Statistically significant correlations were found for renal α-Kg utilization directly with RGP, R_Na, QO₂ and, inversely, with NH₄ + excretion. RGP also was inversely correlated with NH₄ + excretion. QO₂ was correlated with R_Na, but could account for only 60-80% of α-Kg utilized. Increased R_Na was associated with increased glucose utilization. These observations indicate that the renal concentration and metabolism of α-Kg might regulate pathways leading to urinary acidification of Na reabosrption, as well as to RGP. The latter may be a metabolic control device for Na reabsorption. (Supported by NIH grant HD 168-03,04.).

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