Enzymes Structure and Funtion - Done Flashcards
What enzyme catalyses the conversion of pyruvic acid to lactic acid?
LDH - lactate dehydrogenase (enzyme)
Give ways as to how enzymes catalyse reactions
Provide a reaction surface (active site) - weakening of high-energy bonds
Provides a suitable environment (hydrophobic)
Brings reactants together - holds substrate in correct orientation to increase the chances of reaction
Enzymes catalyse both forward and backward reactions
Provide acid/base catalysis
Provides nucleophilic groups - serine / cysteine
Stabilises the transition state with intermolecular bonds
What’s the benefit of active sites being more hydrophobic than enzyme surface?
Provides suitable environment for many reactions that would be difficult/impossible in aqueous environment
Define activation energy
The difference between the transition state and the substrate - determines rate of reaction
What is the ∆G in reaction pathways?
The difference in energy between the starting material and the product
∆G doesn’t change when using enzyme or not
What equation gives the energy difference of reaction pathways?
E = ∆G = -RTlnK
What equation gives the rate constant of a reaction?
Rate constant = k = A exp(-E/RT)
How do you find the equilibrium constant K?
K = [products] / [reactants]
What does hydrogen bonding take place between?
An electron-deficient hydrogen and an electron-rich heteroatom (N or O)
How is hydrogen bonding unlike other intermolecular forces?
Involves orbitals and is directional
Optimum orientation is 180˚ between X, H and Y
Give 2 examples of strong HBAs
Carboxylate ion and phosphate ion
Give 3 examples of moderate/good HBAs
Moderate:
Carboxylic acid
Amide oxygen
Ketone
Ester
Ether
Alcohol
Tertiary amine - Good
Give 3 examples of poor HBAs
Sulphur
Fluorine
Chlorine
Aromatic ring
Amide nitrogen - lone pair tied up
Aromatic amine - delocalised ring
Give 2 examples of good HBDs
Aminium ion - HNR3
Secondary amine
Primary amine
What’s the importance of dipole moments in drugs?
Dipoles align the drug as it enter the binding site - orienting the molecule
Can be beneficial or detrimental if groups aren’t positioned correctly
How do induced dipole interaction occur? Give an example of this.
Where the charge on one molecule induces a dipole on another
Quaternary ammonium ion and an aromatic ring
What is the role of water in drug binding?
Water solvates the drug and its target, so before binding can happen water must be stripped away.
If energy required to solvate both the drug and binding site is > the stabilisation energy gained by the binding interactions then the drug may be ineffective - ensure ∆G < 0
What’s the problem with hydrophobic interactions and water when binding?
Surrounding water molecules form stronger than usual interactions with each other - more ordered layer of water next to non-polar surface
This represents negative entropy due to an increase in order
Water is freed when hydrophobic regions interact - becoming less ordered and increasing entropy and a gain in binding energy
What is Koshland’s induced fit theory?
Active site changes shape when substrate enters
Substrate induces active site to take up ideal conformation to accommodate it - substrate may also alter its shape to maximise bonding interactions
Enzyme also binds to the transition state, stabilising state and lowering activation energy
How does histidine often provided acid/base catalysis?
Acts as a weak base - both protonated and free forms exist at equilibrium
Show the hydrolysis of peptide bonds catalysed by chymotrypsin.
GN5 pages 9 & 10
What are cofactors?
Additional non-protein substances required by many enzymes for a reaction to take place
What are co-enzymes?
Metal ions or small organic molecules (Zinc & NAD+)
Most bind by ionic and non-covalent interactions
What are prosthetic groups?
Covalently bound co-factors
What co-enzyme does lactate dehydrogenase require?
Nicotinamide adenine dinucleotide (NAD+)
What type of reaction do lyases catalyse?
Addition or removal of groups to form double bonds
What type of reaction do ligases catalyse?
Joining 2 substrates at the expense of ATP hydrolysis
What type of reaction do isomerases catalyse?
Isomerisation and intramolecular group transfer
What is genetic polymorphism and its effect?
Subtle differences in structure and properties of proteins between individuals
Can lead to genetic disease or have an effect on drug therapy - due to differences in metabolism
Why is an allosteric site needed for feedback inhibition?
As product will have undergone many transformations and is no longer recognised by the active site - allosteric site needed
How do kinases control activity within the cell?
By phosphorylation amino acids
- can activate or deactivate enzymes
What is external control?
Usually initiated by external messengers which do not enter the cell
What is the importance of nitric oxide?
Nitric oxide passes through the surface membrane and activates cyclases to generate cyclic GMP - secondary messenger which influences other reactions within the cell.
Hence NO has an influence on a diverse range f processes within the cell
Where do the isozymes of lactate dehydrogenase (LDH) act predominantly respectively?
H predominates in heart muscle
M predominates in skeletal muscle
How many different isozyme of LDH are there?
5
HHHH
HHHM
HHMM
HMMM
MMMM
Their properties differ - reactivity
