Option A - second year

bioorganic & medicinal eqns & little memorisations

What is the linear LINEWEAVER-BURKE eqn?

1/V = K_m/V_max * 1/[S] + 1/V_max

What is the eqn that allows us to calculate K_i from the LINEWEAVER-BURKE eqn?

K_i = [INHIBITOR] / ((larger/smaller) -1)

when is Km = [S], and what does that mean for [E] AND the rate of catalysis?

half the enzyme is bound in ES*

[E] = [ES*

½ Vmax

What is the rate of catalysis of a saturated enzyme?

V = k_cat * [ES*]

What are K_m & K_i defined as?

K_m = Substrate Dissociation constant

K_i = Inhibitor Dissociation constant

What is the effect on K_m & V_max of Competitive Inhibitors AND where do they bind?

K_m INCREASES

V_max STAYS THE SAME

ACTIVE SITE

What is the effect on K_m & V_max of Non-Competitive Inhibitors AND where do they bind?

K_m STAYS THE SAME

V_max DECREASES

DIFFERENT SITE

What is the eqn for enzyme efficiency?

k_cat / K_m

DNA strand start from which end? 5’ or 3’

Start = 5’

End = 3’

Why do all AA’s EXCEPT Gly posses L stereochemistry?

L & D stereochemistry is assigned based on the sterics of L-glyceraldehyde

What is the only AA, that displays R stereochemistry?

Cys due to heavier Sulfur atom

Comparatively define log P & log D?

log P is the partition coefficient measuring the intrinsic lipophilicity of a neutral, unionised compound, whereas log D measures the lipophilicity accounting for ionisation, depending on the pH.

Name the 5 types of drug-target interactions

1. van der Waals

2. π-π interactions

3. Hydrophobic interactions

4. Hydrogen bonding

5. Electrostatic/Ionic bonding

What are the Enthalpic & Entropic losses as we go from:

Drug_(aq) + Protein_(aq) —> Drug + Protein

Enthalpic

• loss of H₂O interactions w/ drug & protein respectively

• energetic changes in Drug & Protein

Entropic

• conformational fuctionality of drug

What are the Enthalpic & Entropic losses as we go from:

Drug + Protein —> Drug-Protein Complex

Enthalpic

• new drug-protein interactions

• energetic changes in protein

Entropic

• H₂O returns to bulk

What is IC₅₀ and what does it mean?

IC₅₀ = Inhibitory concentration, when the drug is working only at 50%

When K_eq = [D], [P] = ? and what does it mean?

[P] = [DP], meaning that only 50% of the protein has been bound.

1/K_{eq =} ?

K_i

ΔG eqn for K_eq vs K_i

ΔG = -RTlnK_eq

ΔG = RTlnK_i

What is the Henderson-Hasselbach eqn?

What is the same eqn rearranged to solve the ratio of [A-] : [HA]?

pH = pKa + log ([A-] / [HA])

[A-] / [HA] = 10^pH-pKa

When pH = pKa what does that mean?

[A-] = [HA], meaning only 50% of the acid has dissociated

state the ionisation of acids & bases when:

pH > pKa

pKa > pH

pH > pKa

• acids = deprotonated (-ve ionised)

• bases = unprotonated (neutral)

pKa > pH

• acids = protonated (neutral)

• bases = protonated (+ve ionised)

what assumption is made with fragmental log P ?

Assumes that log P is an additive metric as long as functionality stays the same

What is the point of metabolism and how is metabolism achieved?

The point is to make the drug much easier for the body to eliminate/excrete. Achieved by increasing the polarity of the drug.

What metabolic processes occur during phase I?

• Oxidation (dealkylation, hydroxylation)

• Reduction

• Hydrolysis

What metabolic processes occur during phase II?

• Glucronidation

• Sulfonation

according to lipinski’s rules a drug will have poor absorption if…

c log P is MORE than 5

Mw is OVER 500

MORE than 5 HBDs

MORE than 10 HBAs

What is the eqn for LIGAND efficiency

LE = -ΔG / N (no of heavy atoms)

give the second eqn to calculate LE?

LE = 1.4pK_i / N

What is the eqn for LipE?

LipE = pKi - log P

OR

LipE = pIC₅₀ - log P

What is the eqn for Volume of distribution?

Vd = dose / [drug] in plasma