PHAR 430 Lecture 3: 3. Phase II Enzymes
Document Summary
Conjugates = the products of phase ii reactions: the products are generally devoid of pharmacological activity and are rapidly excreted. Substrates of phase ii reactions = endogenous compound or a xenobiotic can either be a phase i metabolite or the parent molecule. Chemical moieties transferred onto substrates = common metabolic intermediates: they are generally strongly hydrophilic due to the presence of ionic or highly polar functional groups. Transferases = the enzymes that catalyze phase ii reactions: requires atp (directly or indirectly) to drive the reaction accomplished by activating the conjugating agent or sometimes the substrate to a higher energy intermediate. Uridine diphosphate glucuronyl transferases (ugts) - glucuronide conjugation (glucuronidation) Acetyltransferases (n- and o-acetyl transferases) - acetyl conjugation (acetylation) Glucuronic acid is activated to udp-glucuronic acid then added onto the substrate. The enzyme is low affinity (so many substrates) but high capacity (~unlimited glucuronic acid available) 3"phosphoadenosine-5"- phosphosulfate (paps), then sulfate is transferred to the substrate.
