Biochemically, hippuric acid is produced from
benzoic acid and glycine, which occurs in the liver, intestine, and kidneys. In terms of mechanism, benzoic acid is converted to
benzoyl CoA, an acylating agent. Hippuric acid may be formed from the essential amino acid
phenylalanine through at least two pathways. Phenylalanine undergoes
biotransformation to form an
alpha-keto acid,
phenylpyruvic acid, which can tautomerize to a reactive enol. The benzylic carbon is reactive which undergoes
peroxidation followed by the competing pathways to either react with the alpha carbon subsequently form an
dioxetanol intermediate followed by formation of oxalic acid and benzaldehyde, or, peroxidation can react with the
carboxyl group to form an alpha-keto-beta-peroxylactone intermediate followed by formation of
carbon monoxide,
carbon dioxide, and
benzaldehyde. Alternatively, under certain conditions, phenylpyruvic acid may undergo a redox mechanism, such as
Iron(II) donating an electron, to directly release carbon dioxide, followed by carbon monoxide, for the formation of a stable toluene radical which is resolved by an antioxidant such as ascorbate. In all of the aforementioned cases, benzaldehyde undergoes biotransformation via
CYP450 to benzoic acid followed by conjugation to glycine for formation of hippurate which undergoes urinary excretion. Similarly, toluene reacts with CYP450 to form benzaldehyde. Hippuric acid has been reported to be a marker for
Parkinson's disease. ==Reactions==