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 cortex tubules were incubated in Krebs-Henseleit medium with L-alanine as substrate. The tubules metabolized alanine at high rates and in a dose-dependent manner. Most of the alanine nitrogen removed was recovered as ammonia and to a lesser extent as glutamate. Glucose, lactate and glutamate were also found to be significant products of alanine carbon metabolism. A simple mathematical model allowing one to calculate flux of alanine carbon through the various metabolic steps involved is proposed and applied to data obtained in experiments in which 5 mM [U-14C]-,[1-14C]-, [2-14C]- and [3-14C]alanine were used as substrates in parallel. About 40% of the alanine carbon removed was recovered as CO2 and oxidation of C1 of alanine accounted for most of the CO2 released from alanine. Calculations reveal that the ATP produced exceeded 3.2-fold the ATP consumed in relation to alanine metabolism. It is concluded that, in human kidney, alanine may serve as an energy supplier and as a precursor of glucose and ammonia.