6-1 MECHANISTIC CHEMISTRY Introduction Mechanisms of enzyme-catalyzed reactions have been devised using… o _______________ experiments o protein _______________ studies o studies of _______________ model reactions Extraordinary catalytic ability of enzymes results from simple _______________ and _______________ properties, including the _______________ and proper _______________ of reactants in the active sites of enzymes. _______________, _______________, and _______________ have contributed to the understanding of enzyme mechanisms. Mechanisms A detailed description of the _______________, __________ and even _______________ events that occur during a reaction. Lab techniques include… o _______________ labeled reactants that can be used to trace the path of individual atoms o kinetic techniques measure the changes in the chemical __________ of a reactant or solvent during the reaction o studying _______________ changes that give a 3D view of the process Mechanistic information about the reactants and intermediates must be coordinated with the ___-___ structure of the enzyme. The movement of _______________ is represented by __________, and is the key to understanding enzymatic reactions. Nucleophilic Substitution Nucleophiles and electrophiles are ionic intermediates: o Electron-rich: _______________ (has a __________ charge or lone pairs) o Electron-poor: _______________ During nucleophilic substitution, _______________ usually attack _______________ with their lone pairs, called nucleophilic _______________. o For example: o The dissociation of the tetrahedral intermediate (displacement of the leaving group) is the rate-determining step: R=k[ ] o Therefore, there is one reactant molecule in the rds, making it an _____ mechanism. o Serine proteases use _____ mechanisms. Another version of nucleophilic attack involves the making and breaking of two covalent bonds in the transition state: o The formation of the transition state is the rds: R=k[ ][ ] o Therefore, there are two reactant molecules in the rds, making it an _____ mechanism. Cleavage Reactions Covalent bonds can be cleaved in two ways: o Both electrons stay with one atom. For example… _______________ formation: _______________ formation: o One electron remains with each product. For example… __________-_______________ formation: This is not very common in biochemistry. Oxidation – Reduction Reactions Redox reactions are the central to the supply of biological __________. o Oxidation: __________ of electrons. Causes the _______________ of the other reactant, so it is known as the _______________ agent (__________ electrons). o Reduction: __________ of electrons. Causes the _______________ of the other reactant, so it is known as the _______________ agent (__________ electrons). Examples: o _______________ catalyze redox reactions. o _______________, or the removal of hydrogen, is the most common form of biological oxidation, and is catalyzed by _______________.