Glucuronidation

Metabolism of xenobiotic compounds consists of phase I and a phase II biotransformation reactions, being compound modification and conjugation reactions respectively. In phase I biotransformation, the compound is modificated via oxidation, reduction, hydrolysis, or other minor reactions, to reveal a reactive group to which a conjugation molecule can react to. In phase II, a small conjugation molecule reacts with the phase I modified molecule, producing a much more water-soluble molecule that can be excreted more easily. Glucuronidation is a phase II biotransformation reaction in which glucuronide acts as a conjugation molecule and binds to a substrate via the catalysis of glucuronosyltransferases. First, in a series of reactions the cosubstrate uridine diphosphate glucuronic acid (UDPGA) is formed. The glucuronosyltransferases (UGTs) then catalyze the transfer of glucuronic acid from UDPGA to a substrate resulting in a glucuronidated substrate and leaving uridine 5'-diphosphate. UGTs are a very broad and divers group of enzymes and count as the most significant group of conjugation enzymes in xenobiotic metabolism, qualitatively because glucuronic acid can be coupled to a large diversity of functional groups and quantitatively because of the large and divers number of substrates that are formed.

异生物化合物的代谢过程包括Ⅰ相和Ⅱ相的生物转化反应，分别对应化合物的修饰和结合反应。在Ⅰ相生物转化过程中，化合物通过氧化、还原、水解或其他轻微反应被修饰，从而暴露出能够与结合分子反应的活性基团。在Ⅱ相中，小型的结合分子与Ⅰ相修饰后的分子发生反应，生成水溶性更高的分子，从而更容易被排出体外。葡萄糖醛酸化是Ⅱ相生物转化反应之一，其中葡萄糖醛酸充当结合分子，通过葡萄糖醛酸基转移酶的催化作用与底物结合。首先，在一系列反应中，辅底物尿苷二磷酸葡萄糖醛酸（UDPGA）形成。随后，葡萄糖醛酸基转移酶（UGTs）催化葡萄糖醛酸从UDPGA转移到底物上，从而形成葡萄糖醛酸化底物，并留下尿苷5'-二磷酸。UGTs是一组非常广泛且多样化的酶，在异生物代谢中被誉为最重要的结合酶组，从定性角度看，因为葡萄糖醛酸可以与多种多样的官能团结合；从定量角度看，因为形成了大量且多样化的底物数量。