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.