Biochemistry Revision Questions

Question 1

Explain why ionic interactions are stronger in hydrophobic environments than polar environments

Answer 1

Water (a polar solvent) is not present to shield the charges, and so electrostatic attraction is more pronounced

Question 2

Why do alpha helices return to the same location every 7 residues?

Answer 2

Every 7 residues, the alpha helix completes two full turns and so the side chains align perfectly again

Question 3

Label Vmax and Km on a Michaelis-Menten plot

Answer 3

Y axis - reaction velocity
X axis - [substrate]
Vmax - maximum velocity
Km - substrate concentration at 1/2 Vmax

Question 4

How does a non-competitive inhibitor affect Vmax and Km?

Answer 4

Reduces Vmx, and Km remains the same

Question 5

A drug is very polar and poorly absorbed in the gut. Suggest a strategy to improve its bioavailability

Answer 5

Form a prodrug or create a salt if the compound is ionisable. Goal is to increase lipophilicity and passive membrane permeability

Question 6

What is the role of the cytochrome P450 enzymes in drug metabolism?

Answer 6

They oxidise drugs during Phase I metabolism, often making them more polar for excretion. Responsible for drug clearance and can be inhibited or reduced by other drugs

Question 7

How does bacterial resistance to aminoglycosides arise?

Answer 7

Arises when bacteria evolve enzymes that modify the drugs structure, preventing binding to the ribosomes

Question 8

What is the difference between phenotypic screening and target-based drug discovery?

Answer 8

Phenotypic screening focuses on the observable effects a drug has on a cell or organism without knowing the target. Target-based begins with a known target and designs molecules to modulate its function

Question 9

What factors influence if a molecule is a good drug candidate in the early stages?

Answer 9

Selective, stable in the body, easy to synthesise, soluble, permeable, low toxicity

Question 10

What is meant by the structure-activity relationship (SAR)?

Answer 10

SAR is the analysis of how different chemical structures affect biological activity. Helps identify which parts of a molecule are essential for binding/function

Question 11

Why are binding site mapping and docking useful in drug design?

Answer 11

Binding site mapping identifies important regions of a target protein that interacts with ligands. Docking simulates how a molecule fits into this site, predicting binding strength

Question 12

What is meant by bioassay, and what makes a good one?

Answer 12

A bioassay is a test that measures the effect a drug has on a biological system. Good bioassay is simple, fast, specific, and reproducible

Question 13

What is first pass metabolism and how does it effect drug concentration?

Answer 13

Breakdown of drug in liver before it reaches the systemic circulation, reducing its effective concentration

Question 14

What is the difference between transcellular paracellular absorption?

Answer 14

Transcellular occurs through cells via diffusion. Paracellular occurs between cells through tight junctions and is limited to small, hydrophilic molecules

Question 15

Why is membrane fluidity important for drug absorption and cellular function?

Answer 15

Membrane fluidity affects how easily molecules like drugs can move within or through the membrane

Question 16

What is meant by CYP induction and inhibition?

Answer 16

Induction increases the amount of enzyme, speeding up metabolism and reducing drug levels. Inhibition blocks activity, slowing metabolism, and increasing drug levels

Question 17

Define resistance and give some molecular mechanisms by which it can occur

Answer 17

Resistance is the ability of organisms to survive exposure to a drug that would normally harm/kill them. Mechanisms include drug efflux pumps, enzyme-mediated degradation, target mutation, and reduced drug uptake

Question 18

What is meant by cytotoxicity, and how can it be controlled in treatment?

Answer 18

Cytotoxicity is the ability of a substance to kill cells. Controlled by only targeting rapidly dividing cells, specific delivery, and dosing carefully to balance efficacy and safety.

Question 19

What does signal transduction invlove?

Answer 19

Receptors that convert extracellular signals into intracellular responses

Question 20

What are the two main types of receptors?

Answer 20

G-Protein-Coupled Receptors, and Kinase Receptors

Question 21

How does the G-protein coupled Receptor work?

Answer 21

Binding of ligand, activation of G-protein, alpha subunit separates, triggers downstream signalling

Question 22

Define signal amplification in terms of the G-protein-Coupled receptor

Answer 22

one ligand can activate many G proteins

Question 23

How does the kinase receptor work

Answer 23

ligand binding, direct activation of kinase domain inside cell

Question 24

Define agonist

Answer 24

binds to and activates the receptor, triggering a response via conformational changes to the active site

Question 25

Define antagonist

Answer 25

binds to but does not activate, so no response

Question 26

Define partial agonist

Answer 26

binds to and activates the receptor, but produces submaximal response

Question 27

Define inverse agonist

Answer 27

reduces any baseline activity of the receptor

Question 28

how would you make a drug more lipophilic?

Answer 28

Add non-polar groups, reduce hydrogen bond donors and acceptors, decrease ionisable groups

Question 29

how would you make a drug more hydrophilic?

Answer 29

add polar groups, add ionisable groups, form a salt

Question 30

how to increase resistance to phase I metabolism?

Answer 30

avoid structures easily oxidised by cytochrome P450, add steric hinderance, modify/block oxidation prone groups

Question 31

how to improve activity by ridigification?

Answer 31

introduce rings or double bonds to reduce flexibility, lock molecule in conformation close to its active form to reduce entropy loss upon binding = stronger binding