Rate equations and kinetics of uptake of alpha-aminoisobutyric acid and gamma-aminobutyric acid by mouse cerebrum slices incubated in media containing L(+)-lactate or a mixture of succinate, L-malate, and pyruvate as the energy source

Abstract

Influx of alpha-aminoisobutyric acid (AIB) and gamma-aminobutyric acid (GABA) by mouse cerebrum slices incubated with L-lactate or a mixture of succinate, L-malate, and pyruvate (SMP) as the energy source follows the phenomenological rate equation for influx from pyruvate and glucose media: v = Vmax/(1 + Kt/S) + kuS, where v is rate and S is concentration of amino acid. There are two kinetically distinct, parallel components for concentrative uptake, one saturable, and one unsaturable. Rates are less with lactate than with pyruvate and still less with SMP (only GABA was studied), disproving the hypotheses that lower rates with pyruvate compared to glucose are due to an abnormal redox state in the tissue or to a Krebs cycle unbalanced by input at only one point. The carriers for AIB and GABA are qualitatively different. In lactate medium the capacity of each AIB carrier is unchanged but its affinity is reduced to one-third. In lactate and SMP media, the capacity of the saturable GABA carrier is diminished although its affinity is increased. Rates from these media with added glucose or a glucose analog confirm that amino acid and glucose fluxes are not coupled.