Hippuric acid crystallizes in
rhombic prisms which are readily soluble in hot water, melt at 187 °C, and decompose at about 240 °C.[2] High concentrations of hippuric acid may also indicate a
toluene intoxication; however, scientists have called this correlation into question because there are other variables that affect levels of hippuric acid.[3] When many aromatic compounds such as
benzoic acid and
toluene are taken internally, they are converted to hippuric acid by reaction with the
amino acid,
glycine.
Biochemically, hippuric acid is produced from
benzoic acid and glycine, which occurs in the liver, intestine, and kidneys.[5] In terms of mechanism, benzoic acid is converted to
benzoyl CoA, an acylating agent.[6]
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.[7] Similarly, toluene reacts with CYP450 to form benzaldehyde.[8]
^Chiba, M.; Poon, K.; Hollands, J.; Pang, K. S. (1994). "Glycine Conjugation Activity of Benzoic Acid and its Acinar Localization in the Perfused Rat Liver". The Journal of Pharmacology and Experimental Therapeutics. 268 (1): 409–416.
PMID8301581.
^Hopper, Christopher P.; De La Cruz, Ladie Kimberly; Lyles, Kristin V.; Wareham, Lauren K.; Gilbert, Jack A.; Eichenbaum, Zehava; Magierowski, Marcin; Poole, Robert K.; Wollborn, Jakob; Wang, Binghe (2020-12-23). "Role of Carbon Monoxide in Host–Gut Microbiome Communication". Chemical Reviews. 120 (24): 13273–13311.
doi:
10.1021/acs.chemrev.0c00586.
ISSN0009-2665.
PMID33089988.
S2CID224824871.
^Liebig, Justus (1829).
"Ueber die Säure, welche in dem Harn der grasfressenden vierfüssigen Thiere enthalten ist" [On the acid which is contained in the urine of grass-eating, four-footed animals]. Annalen der Physik und Chemie (in German). 17 (11): 389–399.
Bibcode:
1829AnP....93..389L.
doi:
10.1002/andp.18290931104. Liebig named hippuric acid on p. 390: "Da ich die Säure aus dem Pferdeharn vorzugsweise untersucht habe, so werde ich sie, in Ermanglung eines passenderen Namens, mit Hippursäure bezeichnen." (Since I have especially investigated the acid from horse urine, then, for want of a more suitable name, I will designate it with [the name] "hippuric acid".)