PathwayStep2701 PathwayStep2722 PathwayStep2727 PathwayStep2733 PathwayStep2744 PathwayStep2755 Methylation Glutathione conjugation Phase II conjugation Authored: Jassal, B, 2004-11-29 11:42:34 Edited: Jassal, B, 2008-05-19 12:57:01 GENE ONTOLOGYGO:0006805 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. Pubmed11805192 Reactome Database ID Release 43156580 Reactome, http://www.reactome.org ReactomeREACT_6959 Glucuronidation Cytosolic sulfonation of small molecules Acetylation Amino Acid conjugation