Amino acid conjugation of benzoic acid

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).

尽管氨基酸共轭反应是人类首次证明的共轭反应，但作为外源羧酸类异生物的代谢途径，氨基酸共轭反应尚未得到充分研究。这主要是因为可供氨基酸共轭反应的异生物底物数量有限且结构多样性不足。与定位于内质网的CYP酶和尿苷二磷酸葡萄糖醛酸转移酶不同，氨基酸共轭反应的酶类位于线粒体中。在药物代谢途径中，氨基酸共轭反应独具特色，其初始过程为形成异生物酰基辅酶A硫酯，随后主要与甘氨酸在人体内进行共轭。在人类首次代谢研究中，外源性苯甲酸在人体内通过共轭反应代谢为马尿酸。