Structure and Function Flashcards
Explain the Lock and Key model
interaction between an enzyme and a substrate which in turn produces a product/s. The model states that an enzyme is specific to which substrate it can attach to and enable it to perform its catalytic function (The substrate is the key and the enzyme is the lock)
- The active site on the enzyme molecule forms a “keyhole” into which the substrate(s) fit like a key. If the enzyme is denatured, it loses its basic shape, and the “key” will no longer fit- the enzyme loses its ability to function.
What is an enzyme
proteins that catalyse chemical reactions within the body (lower the Ea) (provide reaction surface and environment) (position reactants in optimum position for reaction to occur) (weakens bonds)
It is not used up in the process
What is the induced fit model
substrate is not ideal shape for active site so active site is forced to change so substrate can fit (change in shape by maximisation of intermolecular binding interactions)
What is a Reversible inhibitors
enzyme function relies on a balance of binding interactions
What is competitive binding
drug designed to strengthen interactions which inhibit on/off switch enzyme function
what is irreversible inhibition
binds irreversibly to the active site by forming covalent bonds with amino acid residues
What is uncompetitive inhibition
inhibitors bind reversible to the enzyme-substrate complex
What is non-competitive inhibition
inhibitors bind to allosteric site to inhibit enzyme activity but do not inhibit substrate binding
what is a receptor
protein molecules embedded within the cell membrane with part of the structure on the outside of the cell (needed for communication pathways in body)
define Ion-channel receptors
control the movement of ions across cell membrane (made up of protein sub units which traverse the cell membrane) (lock and key)
what is a G-protein-coupled receptor
respond to hormones and slow acting neurotransmitters (membrane-bound proteins activate membrane-bound enzymes through G-protein signalling) (induced fit)
what is a kinase-linked receptor
receptors that can activate enzymes directly (protein contains both receptor binding site and enzyme active site)
what is an agonist
mimic natural substrate and need to bind to receptor to activate it
what is antagonist binding
antagonist bind to receptor and does not activate it (lock and key model used)
what are Transport proteins
proteins that carry polar molecules across cell membrane
What is intramolecular bonding
bonding within the same molecule – including covalent bonding
what is intermolecular bonding
bonding within two neighbouring molecules – non-covalent (involved in drug binding interactions)
what are electrostatic interactions and what is the bond strength
ionic interaction between groups carrying opposite charges (strength is proportional to distance and dependent on pH and salt concentration) (hydrophobic env. Is more favourable) (bond strength = 20-40kJ/mol)
what is hydrogen bonding and what is the bond strength
interaction between electron rich atom and electron deficient atom (electron deficient hydrogen is bonded to an electronegative atom which induces a partially charged hydrogen) (HYDROGEN BOND DONOR DONATES THE HYDROGEN ATOM AND HYDROGEN BOND ACCEPTOR USES THE LONE PAIR TO ACCEPT THEM) (INVOLVES AN ORBITAL OVERLAP) (Bond strength = 16-60kJ/mol) (strength dependent on functional groups involved)
What is the bond strength of van der Waals interactons? How much significance do VDW’s forces have
weak forces (2-4kJ/mol) but when adding the forces up together it can have a significant effect. (occurs in hydrophobic regions)
what are dipole-dipole interactions
polarization of a bond by presence of an electronegative atom produces a permanent dipole – interaction between dipole within drug and dipole in a target site (correct orientation of dipoles results in stronger interactions and drug binding affinity)
What are ion-dipole interactions
interaction of permanent dipole on one molecule with an ionic charge on another
What is a primary protein
refers to the unique sequence of amino acids in the protein.
order in which amino acids are linked through peptide bonds (peptide bond is planar due to resonance and trans conformer favoured due to steric hindrance)
What is a secondary protein
the coiling or bending of the polypeptide into sheets is referred to the proteins secondary structure. alpha helix or a beta pleated sheet are the basic forms of this level. They can exist separately or jointly in a protein.
what is a tertiary protein
The folding back of a molecule upon itself and held together by disulfide bridges and hydrogen bonds. This adds to the proteins stability
The 3D structure is determined by the primary structure (either covalent or non-covalent)
What is a quaternary protein
Complex structure formed by the interaction of 2 or more polypeptide chains.
proteins can be made from protein subunits held together by intermolecular bonding (ionic bonding, hydrophobic and van der Waals interactions are most important interactions)
What is the main ingredient of antifreeze?
What is the main ingredient oxidised to?
How does oxidation occur?
Explain the inhibition of the main ingredient of antifreeze?
The main ingredient of antifreeze is ethylene glycol which is oxidised to oxalic acid
Oxalic acid is a toxic substance, and when blocked, it allows recovery from antifreeze poisoning.
Oxidation occurs by alcohol dehydrogenase (ADH)
Ethylene glycol is a natural substrate for ADH. Increasing the natural substrate (ADH), increases the competition for active substrate and so inhibits ethylene glycol binding. Oxalic production is then inhibited and so ethylene glycol will eventually be excreted
What does noradrenaline inhibit and what happens when increasing/decreasing levels of noradrenaline?
Noradrenaline inhibits tyrosine hydroxylase. Increasing levels of noradrenaline leads to an increase in binding to the allosteric site on tyrosine hydroxylase. Decreasing noradrenaline levels leads to a decrease in binding to allosteric site and so production will start again.
What is a sulfonamide?
It is a competitive inhibitor of dihydropteroate synthase and block biosynthesis of tetrahydrofolate in bacterial cells.
What is tetrahydrofolate used for
Tetrahydrofolate is used during synthesis of pyrimidine building blocks in DNA synthesis and so synthesis of cell walls stop growth and division.
However, in human cells they NEED tetrahydrofolate which comes from a different pathway which is absent in bacterial cells.
What does sulfonamide mimic?
Sulfonamide mimics PABA (p-aminobenzoic acid) for dishydropteroate synthetase
How do cells build up resistance?
cells build up resistance through increased synthesis of p-aminobenzoic acid (PABA) and mutation of the enzymes active site to lower affinity to sulfonamides
describe how the receptor is activated.
Receptor surfaces has a shape which contains selective binding sites for chemical messengers. When binding, the substrate does not undergo a chemical reaction.. Instead, binding the messenger leads to induced fit (active site must change). So when shape of binding site is changed, the shape of protein also changes which leads to transmission of messages.
