人尿苷二磷酸葡醛酸转移酶1A6重组酶对酚类和羧酸类化合物与葡醛酸结合的催化活性

Catalytic activities of recombinant human uridine 5′-diphosphate glucuronosyltransferases 1A6 on glucuronidation of phenols and carboxylic compounds

目的利用杆状病毒系统表达的人尿苷二磷酸葡醛酸转移酶(UGT)1A6重组酶对一些化合物进行葡醛酸结合研究,以筛选或验证UGT1A6重组酶的底物。方法采用HPLC法对底物或代谢物进行检测,并根据底物的减少来计算该酶对各底物的酶动力学参数。结果人UGT1A6重组酶能很好地催化α-萘酚、β-萘酚和儿茶酚的葡醛酸结合,但对托特罗定、对乙酰氨基酚、水杨酸、对氨基水杨酸、槲皮素、山奈酚、异鼠李素、扁桃酸、布洛芬和萘普生无明显催化活性。结论人UGT1A6重组酶对平面的简单酚类化合物有明显的催化活性,但对结构复杂的酚类或羧酸类化合物活性不明显。

AIM To screen or validate the substrates of uridine 5＇-diphosphate glucuronosyltransferases （UGT）1A6 with a recombinant human UGT1A6 expressed by baculovirus expression system. METHODS Using HPLC to detect the substrates or metabolites, and calculating kinetic parameters of the recombinant UGT1A6 toward each compound. RESULTS The recombinant human UGT1A6 could well catalyze α-naphthol, β-naphthol and catechol markedly, but could not catalyze tolterodine, acetaminophen, salicylic acid, p-aminosalicylic acid, quercetin, kaempferol, isorhamnetin, mandelic acid, ibuprofen and naproxen. CON-CLUSION The recombinant human UGT1 A6 can catalyze simple planar phenols, but not complex phenols or carboxylic compounds.