Enzymes and Catalysis Flashcards
In what ways do enzymes interact with substrates?
Substrates usually interact with the protein amide backbone and side chains, and must also physically fit into the binding site
3 main molecular interactions:
- Hydrogen bonding
- Hydrophobic forces
- Ionic interactions
How does hydrogen bonding play a role in enzyme/substrate binding?
If the substrate is incorrect or not oriented properly, the interaction will be unfavourable due to the loss of hydrogen bonds
- Note that H bonding is strongest when the H is more acidic and the lone pair is more basic
- Also note that H bonding adds 5-10 kcal of energy per mole but NOT to the substrate-protein binding energy
How do hydrophobic forces play a role in enzyme/substrate binding?
The expulsion of water from non-polar regions is entropically favoured as it creates disorder
- Hydrophobic regions come together not due to attraction but because the process is entropically driven
How do ionic interactions play a role in enzyme/substrate binding?
Ionic interactions can pull the substrate and enzyme together favourably
- Ionic interactions are attractions of opposite charges
- Larger charge = greater attraction
Describe how chirality influences enzyme/substrate binding
- Amino acids are chiral, so enzymes are chiral molecules
- Chiral molecules interact differently with other chiral molecules (enzymes can recognise one stereoisomer over the other)
How does an enzyme interact with achiral substrates?
- They transform them into chiral products
- An achiral substrate is therefore called ‘prochiral’
Enzymes accelerate rates of reactions by reducing activation energy. State 6 ways this can be done
- Orient the reacting functional groups
- Provide a solvent environment that favours the chemical reaction
- Perform a complex reaction in a series of smaller steps
- Bind the transition state very well to stabilise
- Act as acid or base catalysts
- Form covalent bonds with the substrate after initial binding
- I.e., changing the reaction from inter to intramolecular
How do proximity and orientation influence enzyme/substrate reaction rates?
- Explain the impact of degree of freedom
Enzymes can increase reaction rates by bringing substrates/reactants together in close proximity
- Degree of freedom: number of possible ways two bonds can be moved away from each other
Why must hydrolysis of peptides in our body be enzyme catalysed?
- Amide bonds are stable (half life t1/2 = 500 years)
- Hydrolysis requires a base to form a tetrahedral intermediate
- An enzyme must bring the base (Enz-OH) as biological pH = 7
- The tetrahedral intermediate must be stabilised by hydrogen bonding to an enzyme backbone
- The amide is a poor leaving group and requires protonation by an enzyme
What are cofactors and coenzymes?
Many enzymes require additional non-protein components called cofactors
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Cofactors can be inorganic ions (ex., Mg2+, Zn2+) or small organic molecules called coenzymes (vitamins)
- Coenzymes may donate/accept a portion of their structure to/from the starting material, intermediate, or product