How do enzymes catalyse reaction Flashcards
Where does enzyme substrate binding occur?
The active site
Active site has amino acid side chains projecting into it. Side chains bind to substrates via several/multiple weak interactions. Determines specificity of the reaction - important as you need enzymes to be doing the right reaction at the right time
Why are weak bond advantageous?
Multiple weak bonds are required for substrate binding. The weak bonds can only form if the relevant atoms are precisely positioned. It is easier to break weak bonds.
What is molecular complementarity?
Molecular complementarity is achieved through combination of these weak bonds and are crucial between enzyme and substrate. Some enzymes are extremely specific and some have a wider range of substrate
What are the 4 types of enzyme substrate bonds?
Ionic bonds (salt bridges) make use of charged side chains (Asp, Glu, Arg and Lys). Hydrogen bonds can be formed by side chain residues or backbone O and N atoms and can often act as hydrogen bond donors and acceptors. Van der Vaal reactions form between any protein and substrate atoms in close proximity; weakest of the interactions. Covalent bonds are relatively rare; much stronger than the other bonds
How can enzymes show stereospecificity?
Provided the shape of the active site is asymmetric and same size, the enzyme can distinguish between identical groups on the substrate - stereospecificity - can only bind in correct orientation
What are the two models for enzyme-substrate binding?
Emil Fischer : lock and key model, shape of substrate and conformation of active site are complementary to each other
Dan Koshland : induced-fit model, enzyme undergoes a conformational change upon binding to substrate, shape of active site becomes complementary to shape of substrate only after substrate binds to enzyme
How is activation energy lowered?
Ground state destabilisation, transition state stabilisation or by providing alternate reaction pathway with a different lower energy transition state
What are the 5 catalytic mechanisms?
Preferential binding of the transition state
Proximity and orientation effects
Acid-base catalysis
Metal ion catalysis
Covalent catalysis
Preferential binding of transition state
An enzyme should bind the transition state more tightly than it binds the substrate
Need to design, synthesis and analogue the transition state - key principle is trying to mimic the transition state e.g. lipitor
Proximity and orientation effects
For two molecules to react they need to be close together and in the correct orientation
Acid-base catalysis
Acid base catalysis involves proton transfer -> side chains that can donate or accept a proton (charged side chains)
pKa of side chain Glu, Asp is 4
pKa of side chain Lys, Arg is 10 and 12
Metal ion catalysis
Metal ions are often required for catalytic activity as they provide: Correct substrate orientation due to specific coordination geometry, ability to act as lewis acid (good electron acceptor) hence can polarise water or other functional groups and sites for electron transfer (oxidation and reduction reactions)
Covalent catalysis
Involves formation of reactive, short-lived intermediate that is covalently attached within enzyme active site - needs to be transient
