Enzyme Inhibition

Question 1

enzyme inhibition

Answer 1

ligand binds and diminishes catalysis

Question 2

aspirin vs ibuprofen

Answer 2

ibuprofen 1/2 life is 24 hours, so it dissociates from COX and platelets can clot again; aspirin has a 1/2 life of 10 days and platelets have a life of 7-10 days, so process is essentially irreversible

Question 3

penicillin

Answer 3

Penicillin irreversibly inhibits the enzyme transpeptidase by reacting with a serine residue in the transpeptidase. This reaction is irreversible and so the growth of the bacterial cell wall is inhibited.

Question 4

penicillin resistance

Answer 4

beta lactamase hydrolyzes penicillin

so new penicillins are poorer substrates OR beta lactamase can be irreversibly inhibited by augmentin (clavulinic acid)

Question 5

Serpins

Answer 5

serine protease inhibitors
irreversible suicide inhibitors; use conformational change to inhibit proteases;
protease flips on itself and gets stuck

Question 6

clinically important serpins

Answer 6

anti-thrombin
alpha1-antitrypsin
fibrinolysis, tissue remodeling, tumor metastasis, inflammation, apoptosis

Question 7

anti-thrombin

Answer 7

serpin
inhibits coagulation in blood clotting cascade;
regulated by heparin like molecules

Question 8

alpha1- antitrypsin

Answer 8

trypsin (in digestive system-hydrolyzes protein)
inhibits neutrophil elastase in lungs (protective)
inactivated by cigarette smoke
low levels predispose towards emphysema and cirrhosis

Question 9

mercury

Answer 9

irreversibly binds to sulfhydryl groups of cysteine and irreversibly inhibits many enzymes

Question 10

lead

Answer 10

lead mimics calcium, a co-factors, and binds and inhibits calmodulin and protein kinase C

Question 11

treatment for heavy metal poisoning

Answer 11

chelation using EDTA

Question 12

irreversible inhibition as a pathology

Answer 12

diabetes- nonspecific glycation destroys activity of enzymes and proteins

Question 13

types of reversible inhibitors

Answer 13

competitive, non-competitive, uncompetitive

Question 14

lineweaver- burke plot

Answer 14

recasting data from michaelis menten plot in a line- easier to visualize effects of inhibitors

Question 15

competitive inhibitio

Answer 15

compete with substrate for the same form of enzyme, often at same site;
affects the binding step;
Vmax does not change and Km does not change- midpoint changes

Question 16

alcohol dehydrogenase

Answer 16

converts alcohol to aldehyde

substrates are ethanol, methanol, and ethylene glycol all which competitively inhibit the reactions of the other two

Question 17

metabolic products of ethanol lead to

Answer 17

hangover

Question 18

metabolic porudcts of methanol and ethylene glycol

Answer 18

death

can use ethanol as a competitive inhibitor

Question 19

non-competitive inhibition

Answer 19

substrate can still bind to enzyme, but enzyme can’t do anything with it because inhibitor is bound somewhere else;
lowers enzyme concentration and lowers Vmax

Question 20

noncompetitive inhibition of heme oxidase (HO)

Answer 20

normally a stress response enzyme which is present in several tumors; inhibitors resemble anti-fungal agents; does ketoconazole inhibit HO?

Question 21

uncompetitive inhibition

Answer 21

inhibitor binds only to enzyme-substrate complex

changes Km and Vmax

Question 22

acytylcholinesterase

Answer 22

hydrolase located in nerve synpases which hydrolyzes acetylcholine
presynaptic neuron release acetylcholine and post synaptic cell binds acetylcholine with receptors (muscarinic and nicotinic)

Question 23

myasthenia gravis

Answer 23

neuromuscular disease;
too few receptors on post synaptic cell and acetylcholinesterase hydrolyzes acetylcholine too quickly; if one blocks acetylcholinesterase, it will allow more time for acetylcholine signal;

use carbamate as drug

Question 24

carbamate

Answer 24

neostigmine; reversible acetylcholinesterase inhibitor
half life of 20 minutes;

can easily overdose and have too much acetylcholine in the synapse

Question 25

carbamate poisoning/overdose

Answer 25

nerve signal is overstimulated and then paralyzed;

compete muscarinic receptors with atropine so that the acetylcholine can’t bind and the atropine complex can’t send signal (mandrake plant)

Question 26

acetylcholinesterase irreversible inhibition

Answer 26

by nerve gas (Sarin) and pesticides;
same reaction as overdose of carbamates however 1/2 life is MUCH LONGER;
take pralidoxime (2-Pam) which is a stronger neucleophile so that the reaction is reversed