IMC 07 and 10: Enzymology Flashcards
What is Gibb’s free energy (G)?
energy portion of a thermodynamic system available to do work
What is acid-base catalysis?
- general acid catalysis: process in which partial proton transfer from Brønsted acid lowers the free energy of a reaction’s transition state
- general base catalysis: process in which partial proton abstraction from Brønsted base lowers the free energy of a reaction’s transition state
What is covalent catalysis?
involves rate acceleration through the transient formation of a catalyst-substrate covalent bond
What is metal ion catalysis?
metal ions participate in catalytic process in three major ways:
- by binding to substrates so as to orient them properly for reaction
- by mediating oxidation-reduction reactions through reversible changes in the metal ion’s oxidation state
- by electrostatically stabilizing or shielding negative charges
What is electrostatic catalysis?
positive and negative charges interacting with each other – charge distributions about the active sites of enzymes are arranged so as to stabilize the transition states of the catalyzed reactions (resembles the form of metal ion catalysis)
- charge distribution in a medium of low dielectric constant can greatly influence chemical reactivity
- in several enzymes, these charge distributions apparently serve to guide polar substrates toward their binding sites so that the rates of these enzymatic reactions are greater than their apparent diffusion-controlled limits
What are proximity and orientation effects (catalytic mechanisms)?
reactants must come together with the proper spatial relationship for a reaction to occur, and this relationship entails proximity and orientation of reactants relative to one another
- when an enzyme brings two molecules together in a biomolecular reaction, it increases their proximity and decreases their entropy, thereby enhancing reactivity
What is SN2 reaction geometry?
the incoming nucleophile optimally attacks its target C atom along the direction opposite to that of the bond to the leaving group
What is preferential binding of the transition state complex?
binding of transition state to enzyme with greater affinity than the corresponding substrates or products
- if an enzyme preferentially binds its transition state, it can be expected that transition state analogs (stable molecules that resemble TS‡ or one of its components) are potent competitive inhibitors of the enzyme
- theory that enzymes bind transition states with higher affinity than substrates has led to a rational basis for drug design based on the understanding of specific enzyme reaction mechanisms
What is the dissociation constant (KD, KS, or KI)?
equilibrium constant for the dissociation of a ligand or substrate (S) from the enzyme (E)
What is the assumption of equilibrium?
assume that k-1»_space; k2 so that the first step of the reaction achieves equilibrium
What is the assumption of steady state?
with the exception of the initial transient phase of the reaction (ms of mixing enzyme and substrate), [ES] remains approximately constant until substrate is nearly exhausted
- [E]T = [E] + [ES]
- d[ES]/dt ≈ 0
What is the Michaelis-Menten equation?
simple mathematical model for describing the formation of product from known [S] and [E]T
What is Vmax?
theoretical maximal rate constant at which the total enzyme concentration can make product
- Vmax = k2 [E]T
What is the Michaelis constant (KM)?
- substrate concentration at which the rate of the reaction is half maximal
- conveniently used as a constant for an enzyme’s affinity for its substrate (compare to dissociation constant KS)
What is turnover number (kcat or k2)?
rate constant for the formation of product from a reaction intermediate (ie. ES)
- this step represents the chemical transformation that occurs in the reaction
