Chemical Catalysis and Binding Flashcards
catalyst
a catalyst alters the rate of reaction by many orders of magnitude, and at the end of the reaction cycle has returned to its original chemical and electronic state.
A catalyst does not alter the equilibrium of a reaction, just its speed.
what is catalytic power? what is the common catalytic power of enzymes?
Catalytic power is defined as the rate of the catalyzed reaction relative to the rate of the uncatalyzed reaction.
Cat power = rate of catalyzed rxn/rate normal rxn
Catalytic power of enzymes is usually in the range of 106 to 1014
relate the equilibrium constant to free energy
∆G’° = -RT ln K’eq
The larger K’eq, the more negative ∆G’°
ligand
a molecule that binds to a protein through many non-covalent interactions
Substrates bind to Enzymes and are converted to Products
energetically, what occurs during substrate binding to an enzyme?
Binding of a ligand to a protein involves the formation of many non-covalent interactions. To achieve this there is an energy penalty in removing bound water molecules from the binding site, and the ligand (desolvation).
desolvation
Binding of a ligand to a protein involves the formation of many non-covalent interactions. To achieve this there is an energy penalty in removing bound water molecules from the binding site, and the ligand (desolvation).
what is the first step in catalysis?
binding of the ligand
what is binding of a ligand to a protein dependent upon?
Binding is a dynamic process, and is concentration dependent, as there is a greater likelihood that two molecules will collide in a productive manner enabling maximal binding interactions to form.
what types of bonding play a role in binding a ligand?
many different non-covalent interactions
“lock-and-key” hypothesis
The complementarity of the binding surfaces leads to enzymes, receptors and antibodies being very specific for certain ligands
“induced fit” hypothesis
Upon initial binding enzymes undergo some level of conformational change to optimize the interactions
combine the “lock-and-key” and “induced fit” models
Not all experimental evidence can be adequately explained by using the so-called rigid enzyme model assumed by the “lock and key” theory. For this reason, a modification called the induced-fit theory has been proposed.
The induced-fit theory assumes that the substrate plays a role in determining the final shape of the enzyme and that the enzyme is partially flexible. This explains why certain compounds can bind to the enzyme but do not react because the enzyme has been distorted too much. Other molecules may be too small to induce the proper alignment and therefore cannot react. Only the proper substrate is capable of inducing the proper alignment of the active site.
explain stereospecificity in enzyme binding
The asymmetric nature of substrate binding sites, due to inherent chirality (L-amino acids) and complexity of protein enzymes, means they are very stereospecific in the chemistry they catalyze.
explain an enzyme’s effect on the equilibrium of a reaction it catalyzes
Enzymes speed up both the forward and backward
reactions equally. Therefore, enzymes do not change the position of equilibirum (i.e. the relative concentrations of X or Y)
(shown: same relative concentration, varying reaction rate)
describe the dissociation constant ( Kd )
In chemistry, biochemistry, and pharmacology, a dissociation constant ( Kd ) is a specific type of equilibrium constant that measures the propensity of a larger object to separate (dissociate) reversibly into smaller components, as when a complex falls apart into its component molecules, or when a salt splits up into its component ions. The dissociation constant is the inverse of the association constant. (Kd = 1/Ka) In the special case of salts, the dissociation constant can also be called an ionization constant.
(shown: a two component system where P is a protein and L is a ligand)
discribe the association constant ( Ka )
Binding is known as the equilibrium constant of association or association constant, Ka.
The units of Ka are M-1.
These are the concentrations at equilibrium.
(shown: a two component system where P is a protein and L is a ligand)
describe Kd and Ka at equilibrium
K<span>a</span> / K<span>d</span> = Keq
what assumptions are made when modelling enzyme kinematics?
- Solutions are behaving ideally, no external factors in the reaction
E + S ⇌ ES ⇌ E + P
Rate1 = K1 [E][S]
Rate2 = K2 [ES]
- Enzyme constants are actually constant
[E] remains constant and is not subject to protein synthesis or degredation
K is actually constant and does not change due to some environmental factor
- S ⟶ P without enzymes is negligible
Vmax
Vmax = k2[E]t
The rate of reaction when enzyme is saturated with substrate. Because the enzyme is saturated, adding substrate will not increase the rate of reaction and the reaction is said to be proceeding at its maxium rate (velocity)
Km
Km is the concentration of substrate which permits the enzyme to achieve half Vmax. An enzyme with a high Km has a low affinity for its substrate, and requires a greater concentration of substrate to achieve Vmax.
Vo = Vmax/2
Units of M
Michaelis-Menten equation
Vo = Vmax[S]/Km+[S]
Kcat
Kcat = Vmax/[E]t
The enzyme’s turnover number, the number of substrates and enzyme can turn to product at its maximum speed, in units of s-1
catalytic efficiency
Kcat/Km
Higher efficiency means faster substrate turnover
Describe the Lineweaver-Burke plot in terms of y=mx+b
y = 1/Vo
m = Km/Vmax
x = 1/[S]
b = 1/Vmax
What is the formula for the Lineweaver-Burke plot?
1/Vo= (Km/Vmax[S])+1/Vmax
What are the four types of enzyme inhibitors?
- Competitive inhibitor
competes with substrate for enzyme binding and prevents formation of the ES complex
- Uncompetitive inhibitor
binds with the substrate at an allosteric site and prevents the enzyme from turning over substrate to product
- Noncompetitive inhibitor
binds to the enzyme and ES complex equally well and decreases Vmax due to less enzyme available, does not effect Km
- Mixed inhibitor
binds to the enzyme and the ES complex BUT has different affinities for each. If the inhibitor preferentially binds to the enzyme, Km increases due to less free enzyme, if the inhibitor binds preferentially to the ES complex, Km and Vmax decrease.
General Acid Catalysis
Transition state is stabilised by proton transfer from an acid to the substrate
General base catalysis
Transition state is lowered by proton transfer from substrate to a base
Concerted general acid-base reaction
Catalyzed reaction involves both general acid catalysis and general base catalysis simultaneously
What amino acid side chains act as general acid-base catalysts?
Asp, Glu, His, Cys, Arg, Tyr, Lys
specific acid-base catalysis
In specific acid catalysis taking place in solvent S, the reaction rate is proportional to the concentration of the protonated solvent molecules SH+. The acid catalyst itself (AH) only contributes to the rate acceleration by shifting the chemical equilibrium between solvent S and AH in favor of the SH+ species.
S + AH → SH+ + A−
Water mediated catalysis
What is the difference between general and specific acid-base catalysis?
Specific acid-base catalysis is solvent mediated; general acid-base catalysis includes all acids and bases in the reaction itself, and thus all contribute to the reaction rate.
Longer explanation:
In specific acid catalysis taking place in solvent S, the reaction rate is proportional to the concentration of the protonated solvent molecules SH+. The acid catalyst itself (AH) only contributes to the rate acceleration by shifting the chemical equilibrium between solvent S and AH in favor of the SH+ species.
S + AH → SH+ + A−
In general acid catalysis all species capable of donating protons contribute to reaction rate acceleration. The strongest acids are most effective. Reactions in which proton transfer is rate-determining exhibit general acid catalysis
