Phase II - Conjugation of compounds

Phase II of biotransformation is concerned with <b><i>conjugation</i></b>, that is using groups from cofactors to react with functional groups present or introduced from phase I on the compound. The enzymes involved are a set of transferases which perform the transfer of the cofactor group to the substrate. The resultant conjugation results in greatly increasing the excretory potential of compounds. Although most conjugations result in pharmacological inactivation or detoxification, some can result in bioactivation. Most of the phase II enzymes are located in the cytosol except UDP-glucuronosyltransferases (UGT), which are microsomal. Phase II reactions are typically much faster than phase I reactions therefore the rate-limiting step for biotransformation of a compound is usually the phase I reaction.<br>Phase II metabolism can deal with all the products of phase I metabolism, be they reactive (Type I substrate) or unreactive/poorly active (Type II substrate) compounds. With the exception of glutathione, the conjugating species needs to be made chemically reactive after synthesis. The availability of the cofactor in the synthesis may be a rate-limiting factor in some phase II pathways as it may prevent the formation of enough conjugating species to deal with the substrate or it's metabolite. As many substrates and/or their metabolites are chemically reactive, their continued presence may lead to toxicity.

生物转化第二阶段涉及的是共轭反应，即利用辅因子中的基团与化合物在第一阶段中存在或引入的功能基团发生反应。参与此过程的酶为一系列转移酶，它们负责将辅因子基团转移到底物上。这种共轭反应显著提高了化合物的排泄潜力。尽管大多数共轭反应会导致药物失活或解毒，但也有一些可能导致生物活化。大多数第二阶段酶位于细胞质中，除了UDP-葡萄糖醛酸转移酶（UGT），它们位于微粒体中。第二阶段反应通常比第一阶段反应快得多，因此，化合物的生物转化速率限制步骤通常是第一阶段反应。第二阶段代谢可以处理第一阶段代谢的所有产物，无论它们是反应性（I型底物）还是非反应性/活性较差（II型底物）的化合物。除谷胱甘肽外，共轭物种在合成后需要被化学激活。在合成过程中辅因子的可用性可能是某些第二阶段途径的速率限制因素，因为它可能阻止形成足够的共轭物种以处理底物或其代谢物。由于许多底物及其/或其代谢物具有化学活性，它们的持续存在可能导致毒性。