Benzoate conjugation, represented by
hippurate synthesis, was measured in hepatocytes isolated from normal and sparse-fur (spf) mutant mice, with X-linked
ornithine transcarbamylase deficiency, to compare the effects of
glyoxylate and
piridoxylate (a hemiacetal of
glyoxylate and
pyridoxine), substituted for
glycine. Various
amino acid precursors of
glycine described in the literature, including
serine,
threonine,
glutamine, and
glutamate, were studied in a similar manner. The role of
glyoxylate and
piridoxylate was also assessed in the renal cortex, in comparison with liver homogenates from normal and hyperammonemic mice. The results indicate the importance of
glyoxylate and
piridoxylate to completely substitute for
glycine (96-115%) in isolated hepatocytes of spf/Y mice, as compared with 53-69% (p less than 0.05) in normal +/Y controls. The mean value of
amino acid precursors to substitute for
glycine in spf mice was
serine 51%,
threonine 29% (p less than 0.05), and
glutamine 9%. In normal mice, only
serine (21%) (p less than 0.01) partly substituted for
glycine, whereas
threonine,
glutamine and
glutamate gave negative values of net
hippurate synthesis. The specific activity of renal cortex for
hippurate synthesis from
glycine,
glyoxylate and
piridoxylate was 3-4 times that of liver homogenates (p less than 0.01 - less than 0.001). A scheme for the transamination of
glyoxylate by
alanine is presented. Besides
alanine, the excess of
glycine,
serine, and
threonine is readily deaminated in the body to take part in gluconeogenic reactions, thus contributing to
hyperammonemia. The cumulative effect of
benzoate conjugation to drain these ammoniagenic precursors through
glycine may be the basis of its
therapeutic effect in
hyperammonemia.