EFFECTS OF GLYCINE AND GLYOXYLATE ON CEREBRAL GLUCOSE-OXIDATION INVITRO

In Patients with nonketotic hyperglycinemia (NKHG), the principal route of glycine catabolism in the CNS is interrupted by an hereditary defect in the glycine cleavage reaction [5, 10‐methylenetetrahydrofolate: ammonia hy‐droxymethyltransferase (decarboxylating, oxidizing); EC 2.1.2.10] (ANDO el al, 1968; Perryet al, 1975). The resulting accumulation of glycine in cerebral tissue of affected infants is invariably associated with the development of severe brain damage, though the mechanism of the damage is still unknown. The rapidity of onset of the condition, which often occurs within a few hours after birth, along with the severity and irreversibility of the cerebral damage, suggests that some critical metabolic process is affected by the accumulation of glycine or one of its normally minor metabolites. The study reported here was undertaken to determine the effects of glycine and its α‐ketoacid metabolite, glyoxylate, on glucose oxidation in immature rat brain slices, and whether glyoxylate accumulation in NKHG might account for the severe brain damage occurring with the disease. The results showed that although glyoxylate markedly inhibited cerebral glucose oxidation in vitro, excess amounts of the compound could not be demonstrated in NKHG brain. Copyright © 1979, Wiley Blackwell. All rights reserved