enzyme catalysis Flashcards
Catalysts
Accelerate the rate of a reaction by lowering the activation energy needed to reach the transition state (TS)
The dont change the free energy of the substrate or product
They dont shift equilibrium of the reaction (no change in Keq)
ONLY the activation energy is lowered
They are not consumed in the reaction
Enzymes are catalysts that determine what happens and how fast it happens
Keq= Product/ substrate it is not affected by catalysts
Thermodynamically favorable means that you make a more stable product (so substrate is less stable than product)- due to the major force of difference of bond energies between substrate and product
Thermodynamics
When a reaction is thermodynamically favorable it means that (Keq> 1) this is never affected by catalysts
A reaction can be kinetically un favorable if the trasition state is high (it will only become fovorable in the presence of a catalyst) which affects the rate constant Kr (and will lower the slope of transition state (lowers activation energy and lowers free energy and lowers T state)
reverse reactions can (but usually dont happen) becacuse you need to add energy
Classes of enzymes
Over The Hill Lies Indecent Lizzie
- Oxido reductases (oxidation Reduction)
- Transferases (group transfer)
- Hydrolases (hydrolysis reactions)
- Lyases (addition and removal of groups from double bonds)
- Isomerases (intramolecular group transter)
- Ligases (ligation of 2 substrates using ATP)
Steps to get to transition state in absence of enzyme
Molecules must be in close proximity (temp and viscosity of solvent)
Reactants need to get caged together by water molecules
Caged reactants must collide with sufficient energy to exceed the activation energy of reaction
Reactants have to collide in correct orientation of therir reactive groups, and water molecules must be moved out of the way (aka desolvation)
How enzymes help catalyze the reaction
Enzymes bind to substrates within thier own active site to bring the approbrate substrates in close proximity
Proximity effect (intra molecular rxs are faster than inter)
Enzymes tightly bind to the TS and reduce the AE
Microenvironment effects
The Functional groups
Acids give protons, bases take protons
pKa= tendency to lose a proton (the lower the pKa, the stronger the acid and the more willing to give up a proton)
Electrophile : electron acceptor/ proton donor
Nucleophile: electron donor/ proton acceptor
Active site micro environment: the amino acid residues lining the active site of an enzyme will impact the pKa of reactive functional groups
Hydrophobicity and Charge
Hydrophobic amino acids on active site= pka of group increases on the S (weakens acid and makes it more basic) (higher pka means less protonation which usually means mor uncharged forms of groups are more favorable)
Charged/ polar aa= pka of group decreases (lower pka means like to be protonated and charged) (more acidic weakens base
other types of catalysis
Metal ion catalysis-> increases reactivity of adjacent atoms by drawing in electrons
Covalent catalysis-> enzyme is the middle man
Serine proteases
Chymotrypsin has a hydrophobic pocket and is used for hydrophobic aa (Phe)
Trypsin has an acidic (Asp) active site is used for basic aa (Lys and Arg)
Elastase has a sterically crowded active site is used for small aa (ala, gly)
Ways that enzymes act as a catalyst
what does the active site do?
What is Kcat
Catalyst types:
Stabilization of transition state (decreases Ea, active site accomodates Tstate better than substrates or products, pharma)
Proximity effects (increasing local concentration)
Microenvironment effects (charged or hydrophobic, differes from solvent)
Acid base catalysis (add/sub protons)
Covalent catalysis (S-E intermediate that is more reactive than S)
Active site:
Substrate specific, proper orientation, exludes H2O, provides reactive groups like cofactors
Kcat: max reaction rate (substrate conversion/second) for a given enzyme
Free energy diagram
dG= free energy dGo= -RTln Keq
What do enzymes effect
Kr (rate of reaction): increased
Ea (activation energy): decreased
Free energy of Substrates/ Prodeucts: NOT CHANGED
Reaction equilibrium (Keq): NOT changed
Keq and dGo
When Keq<1
More substrate than product, thermodynamically unfavorable, and a positive dGo (non spontaneuous)
When Keq>1
More product at equilibrium, thermodynamically favorable, neg dGo (spontaneous
When Keq=1, dGo is 0
Cell respritation formula
C6H12O6 + 6 O2 -> 6 CO2 + 6 H2O + ATP
Metal Ion catalysis
Metal cations increase the electronegativity of nearby atoms by drawing electrons, they are cofactors that activate substrates, by stabilizing the transition state thru ionic bonds
Covalent catalysis
Covalent intermediate is formed between the S and the P called a SE
SE is very reactive and becomes the P and reduces the Transition state activation energy of following reactions to P
