Enzyme - Inhibition

Question 1

Irreversible Inhibition

Answer 1

Is the permanent binding of an inhibitor to an enzyme, typically mimicking substrate binding catalytic centre.

Question 2

What is an example of Irreversible Inhibition?

Answer 2

Acetylsalicyclic Acid
5-Fluorouracul

Question 3

Acetylsalicyclic Acid

Answer 3

This is a nonsteroidal anti-inflammatory drug- reducing signs of inflammation.

Question 4

What does ASA target/inhibit?

Answer 4

Cyclocoxygenase

Question 5

Cyclooxygenase

Answer 5

These are enzymes producing prostaglandins, prostacyclinc and thromboxane converting arachidonic acid to prostaglandin H2

Question 6

What are the two isoforms of Cycloxygenase?

Answer 6

COX-1
COX-2

Question 7

COX-1

Answer 7

This maintains physiological functions like aggregation of platelets being widepsred expressed

Question 8

COX-2

Answer 8

This produces prostaglandins contributing to inflammation, pain and fever induced by inflammatory stimuli

Question 9

What is the mechanism of action for aspirin?

Answer 9

Acetylation nuclephilic attack of Ser-530 hydroxyl gene of the active sites meaning arachidonic acid can no longer bind, inhibiting prostaglandin and thromboxanes production

Question 10

What properties does aspirin have?

Answer 10

Analgesic and Antipyretic occuring by prostaglandin synthesis inhibition and hypothalamus action

Question 11

Analgesic

Answer 11

These are medications used in managment and treatment of pain

Question 12

Antipyretic

Answer 12

These are fever-reducing dtugs

Question 13

How does aspirin inhibit?

Answer 13

Acetyl side group is transferred to the serine residue inhibiting the enzyme permanently despite the competition

Question 14

Arachidonic Acid

Answer 14

This is a polyunsaturated FA being excised from the membrane by phospholipase A2 to act as a substrate

Question 15

What can aspirin be used for?

Answer 15

Prevention of blood clots, which increases heart attack incidence of aspiring are used in tandem with cholesterol reducing agents like statins

Question 16

How may AA apromote platelet aggregation?

Answer 16

Thromboxane A2 when synthesised and produced from AA by COX-1 in platelets

Question 17

5 Fluorouracil

Answer 17

This is a chemotherapy drug inhibiting DNA synthesis by prevetion of pyrimidine base production

Question 18

Thymidylate Synthase

Answer 18

This is an enzyme catalysing deoxyuridine monophosphate to deoxythymidine monophosphate

Question 19

What happens in the catalysis of 5-FLuorouracil

Answer 19

5-FU is converted to dUMP by TS which inhibits TS, otherwise catalysing dUMP conversion to dTMP being a precursor for thyrmidylate.

Question 20

Why is it hard to describe irreverisble inhibition by MMK?

Answer 20

MMK relies on equilibrium below where active enzyme concentration is contanst

Question 21

Reversible Inhibition

Answer 21

This has three categories: competitive, non-competitive or uncompetitive.

Question 22

What does competitive inhibition require?

Answer 22

An inhibitor with low kM so it can bind more effectively than substrate

Question 23

Competitive Inhibition

Answer 23

These are substances combining to the active site of the enzyme being similar in structure to the subrate

Question 24

Methotexate

Answer 24

This is a chemotherapy drug used to treat cancers like leukemia inhibiting Dihydrogolate Reductase required for DNA synthesis

Question 25

What is an example of Competitive Inhibition?

Answer 25

Methotrexate resembling dihydrofolate

Question 26

How does methotrextate competitively inhbiiti Dihydrofolate Reductase?

Answer 26

Competes for hydrogen bond formation within the active site with a higher affinity for the reductase than hydrogolate

Question 27

How can Comp inhibition be represented in an MM graph?

Answer 27

Vmax remains unchanged due to if you add another substrate the inhibition can be outcompeted

Question 28

How does kM increase in competitive inhibition?

Answer 28

Proportional to inhibitory as more the inhibition you have the lower the affinity of the substrate

Question 29

Lineweaver-Burk Plot

Answer 29

This is a graphical representation of the MMK equation

Question 30

Non-Competitive Inhibition

Answer 30

This binds at an allosteric site seperate form the active site of substrate binding, thus regardless of presence of bound substrate

Question 31

What is Vmax in Non-comp Inhibition?

Answer 31

Vmax is reduced, as enzyme cannot reach full velocity because regardless of amount of substrate added the inhibitory cannot be outcompeted

Question 32

What is Km in non-comp inhibition?

Answer 32

Remains unchanged due to fact the affinity of the active site has not changed, only ability to convert the substrate to product

Question 33

Mixed Non-Competitive Inhibition

Answer 33

Affects both substrate binding site and catalysis, so Vmax decrease and Km increase

Question 34

Uncompetitive Inhibition

Answer 34

These bind only to ES compelx not the free enyme

Question 35

What happens in uncompetitive inhibition?

Answer 35

Inhibitor binds to ES and not E

Question 36

What is an example of Uncompetitive Inhibition?

Answer 36

Lithium as a drug treatment for manic depression, inhibiting myo-inositol monophosphatase

Question 37

Whta happens to Vmax in Uncomeptitive Inhibition?

Answer 37

Decrease because substrate is frozen, blocking others getting in as well as cannot be converted to product

Question 38

What happens to Km in Uncompetitive Inhibtion?

Answer 38

Decrease because substrate locked so affinity of the enzyme has increased.