Week 7

Question 1

What are the structure and function of enzymes?

Answer 1

Globular-acts as boys catalyst
Speed up time for reaction to reach equilibrium
Lower the activation energy of a reaction

Question 2

What molecules make up catalytic triad?

Answer 2

Serine 195, histidine 57 and asparteate 102

Question 3

Explain how the catalytic triad acts as a covalent catalysis and acid-base catalysis?

Answer 3

His 57 accepts a proton from Ser 195(acts as a base)

Asp 102 helps orient His 57

Question 4

Enzymes use one of more of these strategies for catalysis…

Answer 4

Covalent catalysis,General acid-base catalysis,Metal ion catalysis,Catalysis by proximity and orientation of two substrates

Question 5

Does carbonic anhydrase employs general acid/base catalysis, metal ion catalysis, and catalysis by proximity and orientation of two substrates?

Answer 5

Yes

Question 6

What does the Zn+ in carbonic anhydrase do?

Answer 6

Zn2+ acts to stabilize the deprotonated form of the water molecule

Question 7

Why is carbonic anhydrase important in blood?

Answer 7

•Carbon dioxide (CO2) is produced from respiring tissues•CO2 must be transported to the lungs to be exhaled•CO2 is hydrated to carbonic acid in red blood cells•Carbonic acid is a weak acid and dissociates to form bicarbonate ions

Question 8

Does the action of carbonic anhydrase help buffer blood?

Answer 8

Yes

Question 9

What is the problem with designing molecules with stronger binding interactions?

Answer 9

Designing molecules with stronger binding interactions results in enzyme inhibitors which block the active site

Question 10

What is a drug target?

Answer 10

Most drugs act on specific proteins or cells in the body, known as the drug target

Question 11

What are the main protein drug targets?

Answer 11

Receptors•Enzymes•Transporters•Ion channels

Question 12

What is reversible inhibition?

Answer 12

Inhibitor bound non-covalently•Prevents substrate from binding •Inhibitor rapidly dissociates from enzyme

Question 13

What is irreversible inhibition?

Answer 13

Inhibitor bound tightly with enzyme•Slow dissociation of enzyme-inhibitor complex•e.g. nerve gases

Question 14

What are the 3 types of reversible inhibitors?

Answer 14

Competitive inhibitors•Noncompetitive inhibitors•Uncompetitive inhibitors

Question 15

What is a competitive inhibitor?

Answer 15

Competitive inhibitors bind to the same site as the enzyme substrate•Hence they compete with the substrate•Chemical structure is therefore similar to the substrate•No reaction takes place on the inhibitor•Inhibition depends on the strength of inhibitor binding and inhibitor concentration

Question 16

What is a non-competitive inhibitor?

Answer 16

Noncompetitive inhibitors bind to a different site from the enzyme substrate•They are allosteric regulators (stabilize an inactive conformation of the enzyme)•Chemical structure is different from the substrate
Effect is not reversed by adding substrate•Often seen in enzymes at the beginning of a metabolic pathway•Inhibitor tends to be a product further down the pathway that then acts to regulate
Irreversible inhibitors permanently inactivate enzymes•Usually form covalent bonds with the enzyme, that cannot be broken

Question 17

How does Orlistat act as an irreversible inhibitor?

Answer 17

Orlistat is an anti-obesity drug that inhibits pancreatic lipase•The enzyme is blocked from digesting fats in the intestine•Fatty acids and glycerol are less absorbed as a result•Leads to reduced biosynthesis of fat in the body

Question 18

How do reversible competitor antagonists work?

Answer 18

Reversible competitive antagonists compete with agonist for binding site on receptors•Hence antagonism can be overcome by adding more agonist•In presence of antagonist, the dose-response curve for an agonist shifts to the right

Question 19

How do irreversible competitive antagonists work?

Answer 19

Bind at same site as agonist, but irreversibly (cannot be released), usually covalently•Adding more agonist cannot overcome effect•Dose-response curve shifts down

Question 20

Enzymes as Drug Targets summary

Answer 20

Some enzymes are allosterically regulated by inhibitors or activators•Enzyme inhibitors can be reversible or irreversible•Irreversible inhibitors usually bind covalently to enzymes•Many important drugs are enzyme inhibitors•Reversible competitive antagonists shift the dose-response curve to the right•Irreversible competitive antagonists shift the dose-response curve down