ALANINE METABOLISM IN ISOLATED HUMAN KIDNEY-TUBULES - USE OF A MATHEMATICAL-MODEL

To gain insight into the fate of alanine nitrogen and carbon taken up by the human kidney under certain conditions, isolated human kidney co rtex tubules were incubated in Krebs-Henseleit medium with L-alanine a s substrate. The tubules metabolized alanine at high rates and in a do se-dependent manner. Most of the alanine nitrogen removed was recovere d as ammonia and to a lesser extent as glutamate. Glucose, lactate and glutamate were also found to be significant products of alanine carbo n metabolism. A simple mathematical model allowing one to calculate fl ux of alanine carbon through the various metabolic steps involved is p roposed and applied to data obtained in experiments in which 5 mM [U-C -14]-, [1-C-14]-, [2-C-14]- and [3-C-14]alanine were used as substrate s in parallel. About 40% of the alanine carbon removed was recovered a s CO2 and oxidation of C1 of alanine accounted for most of the CO2 rel eased from alanine. Calculations reveal that the ATP produced exceeded 3.2-fold the ATP consumed in relation to alanine metabolism. It is co ncluded that, in human kidney, alanine may serve as an energy supplier and as a precursor of glucose and ammonia.