PathwayStep2676 PathwayStep2680 PathwayStep2681 PathwayStep2687 PathwayStep2694 Phase 1 - Functionalization of compounds Authored: Jassal, B, 2008-05-19 12:57:01 Edited: Jassal, B, 2008-05-19 12:57:01 GENE ONTOLOGYGO:0006805 Phase 1 of metabolism is concerned with functionalization, that is the introduction or exposure of functional groups on the chemical structure of a compound. This provides a 'handle' for phase 2 conjugating species with which to react with. Many xenobiotics are lipophilic and almost chemically inert (e.g. PAHs) so would not necessarily undergo a phase 2 reaction. Making them more chemically reactive would facilitate their excretion but also increases their chance of reacting with cellular macromolecules (e.g. proteins, DNA). There is a fine balance between producing a more reactive metabolite and conjugation reactions. There are two groups of enzymes in phase 1 - oxidoreductases and hydrolases. Oxidoreductases introduce an oxygen atom into or remove electrons from their substrates. The major oxidoreductase enzyme system is called the P450 monooxygenases. Other systems include flavin-containing monooxygenases (FMO), cyclooxygenases (COX) and monoamine oxidases (MAO). Hydrolases hydrolyse esters, amides, epoxides and glucuronides. Pubmed12369887 Pubmed16584116 Pubmed17125408 Reactome Database ID Release 43211945 Reactome, http://www.reactome.org ReactomeREACT_13705 Reviewed: D'Eustachio, P, 2008-05-28 08:30:54 Cytochrome P450 - arranged by substrate type FMO oxidizes nucleophiles Amine Oxidase reactions COX reactions Ethanol oxidation