Glycine availability limits maximum hippurate synthesis in growing rats

Abstract

The rate-limiting step for hippurate synthesis from sodium benzoate (NaB) was investigated in growing rats. Rats fed a glycine-and serine-free L-amino acid diet were injected daily with saline or varying doses of NaB. Growth was monitored for 4 d, after which time rats were killed and livers were assayed for glycine, serine, benzoyl-CoA, benzoyl-CoA ligase and glycine benzoyl-CoA transferase. In control animals, liver glycine and serine concentrations were 2.18 and 1.63 mumol/g wet wt, respectively; benzoyl-CoA was not detectable. In rats injected with 600 mg NaB/kg body wt per day, liver glycine and serine concentrations decreased to 68 and 78% of control values, respectively, and benzoyl-CoA accumulated (0.52 mumol/g wet wt). As the dose of NaB was increased, liver benzoyl-CoA concentration increased, and growth of the rats was markedly impaired. The activities of benzoyl-CoA ligase and glycine benzoyl-CoA transferase were unchanged after NaB treatment. In a second experiment, rats were treated with growth-impairing doses of NaB. When the diet was supplemented with serine and glycine, growth was normalized, liver glycine and serine concentrations returned to control levels, and benzoyl-CoA accumulation was markedly diminished. These results suggest that glycine availability limits maximum hippurate synthesis in vivo.