AGE-DEPENDENT ACTIVITY OF L-GLUTAMIC ACID DECARBOXYLASE (GAD) IN HUMAN KIDNEY

The conversion of L-glutamate (L-glu) to y-amino-butyrate (GABA) in mammalian brain & kidney is catalyzed by pyridoxal-phosphate (PLP)-dependent GAD. GABA is an important neuro-inhibitor in CNS, but another role must exist for GABA metabolism in kidney cortex. We assayed GAD by an isotopic method (Lancaster et al, BBA 297:229, 1973) at normal tissue L-glu cone. (4-8mM) ±PLP (0.24mM) in frozen postmortem human kidney obtained between 15wk gestation and lOyr.GAD is stable in tissues or homogenates stored at -20°C; PLP-saturated renal GAD activity is low (<0.5nmoles CO2 formed/rag wet wt·h) before 40wks gestation, then rises at term and plateaus in the infant & child at 5-10x fetal level. Kidney GABA cone, parallels GAD activity. Endogenous GAD activity is often inappropriately low for age, but can be stimulated by PLP in vitro, indicating, undersaturation by co-enzyme in vivo; once bound in vivo, PLP is not easily removed from GAD in vitro. Augmentation of renal GAD activity at term parallels the need for human kidney to extract glutamine from plasma to support renal ammoniagenesis. The GABA pathway permits disposal of the residual glutamate carbon chain as a non-titratable acid.