Amino acid conjugation of benzoic acid (WP521)

Homo sapiens

Despite being the first conjugation reaction demonstrated in humans, amino acid conjugation as a route of metabolism of xenobiotic carboxylic acids is not well characterised. This is principally due to the small number and limited structural diversity of xenobiotic substrates for amino acid conjugation. Unlike CYP and uridine 5′-diphosphate glucuronosyltransferase, which are localised in the endoplasmic reticulum, the enzymes of amino acid conjugation reside in mitochondria. Unique among drug metabolism pathways, amino acid conjugation involves initial formation of a xenobiotic acyl-CoA thioester that is then conjugated principally with glycine in humans. Exogenously administered benzoic acid is metabolised to hippuric acid with a conjugation reaction in humans (as discovered in the first metabolism study in humans).


Lore , Thomas Kelder , Susan Coort , Pieter Giesbertz , Martijn Van Iersel , Martina Summer-Kutmon , Denise Slenter , and Friederike Ehrhart


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Homo sapiens



Pathway Ontology

xenobiotic metabolic pathway glycine metabolic pathway


Label Type Compact URI Comment
hippuric acid Metabolite hmdb:HMDB0000714
Coenzyme A Metabolite hmdb:HMDB0001423
Phosphate Metabolite hmdb:HMDB0001429
Phosphate Metabolite hmdb:HMDB0001429
Acetyl CoA Metabolite cas:72-89-9
glycine Metabolite hmdb:HMDB0000123
ATP Metabolite hmdb:HMDB0000538
Benzoic acid Metabolite chebi:30746
Benzoyl-CoA Metabolite hmdb:HMDB0002252
AMP Metabolite hmdb:HMDB0000045
benzoyl-AMP Metabolite chebi:156046 Benzoic acid AMP ester
GLYAT GeneProduct ensembl:ENSG00000149124
GLYATL2 GeneProduct ensembl:ENSG00000156689
Acyl-CoA synthetase GeneProduct ncbigene:55902
GLYATL1 GeneProduct ensembl:ENSG00000166840


  1. Amino acid conjugation: contribution to the metabolism and toxicity of xenobiotic carboxylic acids. Knights KM, Sykes MJ, Miners JO. Expert Opin Drug Metab Toxicol. 2007 Apr;3(2):159–68. PubMed Europe PMC Scholia