Effect of benzoate on glycine metabolism in rats fed branched-chain alpha-ketoacids

Male albino rats (110-120 g) were fed for 9 days an amino acid diet low in nitrogen (nitrogen, 1.05%) devoid of valine, leucine and isoleucine and supplemented with branched-chain alpha-ketoacids (9.4%) (BCKA diet). Pair-fed controls received an isocaloric diet (AA diet), which contained the three branched-chain amino acids (1.4%) instead of the alpha-ketoacids (nitrogen, 1.2%). A third group was fed a standard diet. The animals were divided into three groups of 12 animals, and 6 animals of each group were injected with benzoate (210 mumol/100 g) for 9 days. On day 10 of the experiment the activity of the glycine cleavage system and glycine concentrations were measured in liver; glycine, serine, ammonia, urea, glutamine and glutamate concentrations were determined in plasma on day 10 and determinations of urinary urea, ammonia, glutamine, glutamate, hippuric acid and benzoate were carried out on days 0 and 10 of the experiment. Feeding BCKA led to an increase of plasma and hepatic glycine levels. Activity of hepatic glycine synthesis was reduced in the BCKA-fed group, whereas compared to the AA-fed group no increase in the decarboxylation activity was observed. Injection of benzoate led to an increase in hepatic glycine decarboxylation and glycine synthesis activity in the BCKA-fed group. Plasma glycine levels did not fall, and there was no change in any of the metabolites measured in urine and plasma.