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尿苷二磷酸-葡萄糖醛酸转移酶(UDP-glucuronosyltransferases,UGT)为II相代谢酶,可催化某些药物与葡萄糖醛酸的结合反应。脑组织UGT表达广泛,但表达量与活性低于肝脏;脑内UGT同样可被诱导或抑制,从而影响药物脑组织的分布和水平;并与细胞色素P450(cytochrome P450,CYP)、转运蛋白密切配合,共同参与、影响某些药物的脑内代谢动力学过程;多种药物以葡萄糖醛酸化产物形式跨越血脑屏障,或以原形在脑内直接生成葡萄糖醛酸化产物,从而发挥各自药理作用。本文简述了UGT脑内亚型、分布、诱导、抑制,与CYP和转运蛋白的相互作用,举例说明某些药物脑内葡萄糖醛酸化过程,旨在为靶向中枢神经系统药物的设计、应用提供研究思路。
Uridine diphosphate-glucuronosyltransferases (UGT) are Phase II metabolic enzymes that catalyze the binding of certain drugs to glucuronic acid. UGT in brain tissue is widely expressed but its expression level and activity are lower than that in liver. UGT in brain can also be induced or inhibited, which affects the distribution and level of drug brain tissue. With the close association of cytochrome P450 (CYP) and transporter Cooperate with, participate in and influence the intracranial metabolic kinetics of certain drugs; many drugs cross the blood-brain barrier in the form of glucuronidation products, or directly produce glucuronidation products in the brain in prototype form, thus exert their respective pharmacological effects. This article describes the subtypes of UGT, its distribution, induction, inhibition, interaction with CYP and transporter, and illustrates the glucuronidation of some drugs in the brain. It aims to design and apply drugs targeting the central nervous system Provide research ideas.