Studies on the valine sensitivity in non-ketotic hyperglycinemia

An oral loading test with L-valine (100 mg/kg body weight) in 3 patients with non-ketotic hyperglycinemia was accompanied by drowsiness and hyperreflexia of the patients. Metabolic studies revealed a slightly lower rate of disappearance of valine from blood in 2 of the patients. In a third patient, the curve was not different from controls. Gas chromatographic analysis for short-chain fatty acids in serum carried out during the valine loading test did not show increased concentrations. Urine collected during the valine loading test did not show excretion of N-acylglycine derivatives. As neither of the branched chain amino acid transaminases proved to be inhibited by glycine, inhibition by glycine of the uptake of valine by the tissues became likely. This uptake has been measured in rat liver slices. Glycine was found to be a competitive inhibitor of valine uptake, with a Ki of 4.9 mM. It is concluded that the tendency to a decreased rate of valine disappearance from blood in non-ketotic hyperglycinemia could be due to an inhibition of valine uptake by the high plasma glycine concentration. The relationship of the inhibited valine uptake in liver slices of rats with the clinical symptoms in non-ketotic hyperglycinemia patients after a valine load remains to be established.