Structure and Function

Question 1

Explain the Lock and Key model

Answer 1

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.

Question 2

What is an enzyme

Answer 2

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

Question 3

What is the induced fit model

Answer 3

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)

Question 4

What is a Reversible inhibitors

Answer 4

enzyme function relies on a balance of binding interactions

Question 5

What is competitive binding

Answer 5

drug designed to strengthen interactions which inhibit on/off switch enzyme function

Question 6

what is irreversible inhibition

Answer 6

binds irreversibly to the active site by forming covalent bonds with amino acid residues

Question 7

What is uncompetitive inhibition

Answer 7

inhibitors bind reversible to the enzyme-substrate complex

Question 8

What is non-competitive inhibition

Answer 8

inhibitors bind to allosteric site to inhibit enzyme activity but do not inhibit substrate binding

Question 9

what is a receptor

Answer 9

protein molecules embedded within the cell membrane with part of the structure on the outside of the cell (needed for communication pathways in body)

Question 10

define Ion-channel receptors

Answer 10

control the movement of ions across cell membrane (made up of protein sub units which traverse the cell membrane) (lock and key)

Question 11

what is a G-protein-coupled receptor

Answer 11

respond to hormones and slow acting neurotransmitters (membrane-bound proteins activate membrane-bound enzymes through G-protein signalling) (induced fit)

Question 12

what is a kinase-linked receptor

Answer 12

receptors that can activate enzymes directly (protein contains both receptor binding site and enzyme active site)

Question 13

what is an agonist

Answer 13

mimic natural substrate and need to bind to receptor to activate it

Question 14

what is antagonist binding

Answer 14

antagonist bind to receptor and does not activate it (lock and key model used)

Question 15

what are Transport proteins

Answer 15

proteins that carry polar molecules across cell membrane

Question 16

What is intramolecular bonding

Answer 16

bonding within the same molecule – including covalent bonding

Question 17

what is intermolecular bonding

Answer 17

bonding within two neighbouring molecules – non-covalent (involved in drug binding interactions)

Question 18

what are electrostatic interactions and what is the bond strength

Answer 18

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)

Question 19

what is hydrogen bonding and what is the bond strength

Answer 19

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)

Question 20

What is the bond strength of van der Waals interactons? How much significance do VDW’s forces have

Answer 20

weak forces (2-4kJ/mol) but when adding the forces up together it can have a significant effect. (occurs in hydrophobic regions)

Question 21

what are dipole-dipole interactions

Answer 21

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)

Question 22

What are ion-dipole interactions

Answer 22

interaction of permanent dipole on one molecule with an ionic charge on another

Question 23

What is a primary protein

Answer 23

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)

Question 24

What is a secondary protein

Answer 24

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.

Question 25

what is a tertiary protein

Answer 25

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)

Question 26

What is a quaternary protein

Answer 26

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)

Question 27

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?

Answer 27

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

Question 28

What does noradrenaline inhibit and what happens when increasing/decreasing levels of noradrenaline?

Answer 28

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.

Question 29

What is a sulfonamide?

Answer 29

It is a competitive inhibitor of dihydropteroate synthase and block biosynthesis of tetrahydrofolate in bacterial cells.

Question 30

What is tetrahydrofolate used for

Answer 30

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.

Question 31

What does sulfonamide mimic?

Answer 31

Sulfonamide mimics PABA (p-aminobenzoic acid) for dishydropteroate synthetase

Question 32

How do cells build up resistance?

Answer 32

cells build up resistance through increased synthesis of p-aminobenzoic acid (PABA) and mutation of the enzymes active site to lower affinity to sulfonamides

Question 33

describe how the receptor is activated.

Answer 33

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.