Glycine and benzoate conjugation and glycine acyltransferase activity in the developing and adult rat: possible relationships to nonketotic hyperglycinemia.

We report investigations of benzoate and glycine metabolism and glycine acyltransferase activity in rats. These studies provide insights related to the therapy and pathophysiology of human nonketotic hyperglycinemia. Liver acyltransferase activity increased sharply postnatally from low levels at birth, but transferase activity was absent in the brain. The enzyme level was unchanged in either organ after administration of 2,3,7,8-tetrachlordibenzodioxin, phenobarbital, benzoate or a high glycine diet. Brain and liver glycine levels remained unaltered during acute or chronic benzoate-induced reductions in plasma glycine levels. Plasma and brain glycine contents were measured in rats at different ages following a single injection of 3 mg glycine/g body weight; after injection, glycine levels in the brain were comparable in severely symptomatic neonatal rats and older asymptomatic rats, suggesting a similar glycine influx but a selective susceptibility of the newborn brain to toxicity from acute hyperglycinemia. When a 3.4% glycine diet was ingested for up to 30 days ad libitum, levels of plasma glycine rose about 4- to 5-fold from those achieved on a diet containing one tenth as much glycine, but brain and liver glycine concentrations increased only 2-fold or less in the chronically hyperglycinemic animals.