Enzyme inhibitors

Question 1

Irreversible inhibitors act at the active site of an enzyme only. True or false?

Answer 1

False - at active site or remote from it

Question 2

An excess of substrate can displace irreversible inhibitors. True or false?

Answer 2

False

Question 3

Cephalosporins are examples of reversible inhibitors. True or false?

Answer 3

False - irreversible

Question 4

Proton pump inhibitors are irreversible inhibitors. True or false?

Answer 4

True

Question 5

Is orlistat a reversible or irreversible inhibitor?

Answer 5

Irreversible

Question 6

Reversible inhibitors bind by intermolecular interactions rather than covalent bonds. True or false?

Answer 6

True

Question 7

Increasing substrate concentration reverses inhibition of reversible inhibitors. True or false?

Answer 7

True

Question 8

Are anti-depressants reversible or irreversible enzyme inhibitors?

Answer 8

Reversible

Question 9

Are ACE inhibitors reversible or irreversible enzyme inhibitors?

Answer 9

Reversible

Question 10

Are statins reversible or irreversible enzyme inhibitors?

Answer 10

Reversible

Question 11

Competitive inhibitors are usually reversible under what circumstance?

Answer 11

If the concentration of substrate is sufficient enough to displace the inhibitor

Question 12

For competitive inhibitors, the inhibition depends on three things. What are they?

Answer 12

The concentration of inhibitor
The concentration of the substrate
The relative affinities of the substrate and inhibitor for the active site of the enzyme

Question 13

A non-competitive inhibitor inhibits at the active site of the enzyme. True or false?

Answer 13

False - adjacent to or distant from the active site

Question 14

Are non-competitive inhibitors influenced by substrate concentration?

Answer 14

No

Question 15

What is Kcat?

Answer 15

Overall rate constant for the decomposition of ES complex into products

Question 16

Substrate analogues and product mimics are ______ ______ inhibitors

Answer 16

ground state

Question 17

Suicide inhibitors and transition state analogues are _______ ______ inhibitors

Answer 17

mechanism based

Question 18

Methotrexate is a competitive reversible inhibitor. True or false?

Answer 18

True

Question 19

Methotrexate has a higher affinity for DHFR than FH2 does. True or false?

Answer 19

True - due to the additional hydrogen and ionic bonds in methotrexate

Question 20

How does methotrexate work in cancer therapy?

Answer 20

It is a competitive reversible inhibitor and so binds to DHFR stopping the pathway to production of N5,N10-methylene-FH4 and so this means there is no source of methyl for production of dTMP = no DNA synthesis and therefore no cell division

Question 21

Methotrexate has a similar structure to FH2. True or false?

Answer 21

True

Question 22

In product mimicking - the final product of the pathway controls the enzyme with the allosteric site. True or false?

Answer 22

True

Question 23

Anti-purine is a product mimic. How does it work as an anti-cancer drug?

Answer 23

It is an analogue of the final product in purine biosynthesis. It is an allosteric inhibitor of an early enzyme in purine biosynthesis

Question 24

6-Mercaptopurine is a prodrug. How does it work as an anti-cancer drug?

Answer 24

It is converted into its corresponding nucleoside mono-phosphate and inhibits the first enzyme in the biosynthesis of purine

Question 25

Product analogues are reversible competitive inhibitors True or false?

Answer 25

False - reversible non-competitive

Question 26

Which three amino acids posses nucleophilic residues that can be attacked by an electrophilic drug to form a covalent bond in irreversible non-competitive inhibition?

Answer 26

Cysteine Serine Histidine

Question 27

What are the three types of irreversible inhibitors?

Answer 27

Suicide inhibitors Affinity labels Group-specific reagents

Question 28

What are group specific reagents?

Answer 28

React with specific AA side chains

Question 29

What are affinity labels?

Answer 29

Reactive substrate analogues Structurally similar to substrate Capable of covalently binding to active site

Question 30

Affinity labels are more specific than group specific reagents. True or false?

Answer 30

True

Question 31

Which drug is an irreversible inhibitor or pancreatic lipase?

Answer 31

Orlistat

Question 32

Irreversible inhibitors are highly reactive. True or false?

Answer 32

True

Question 33

The high reactivity of irreversible inhibitors means they can be hydrolysed and so destroyed by nucleophiles such as GSH. True or false?

Answer 33

True

Question 34

The high reactivity or irreversible inhibitors means that they are likely to be destroyed by attacking other cellular components e.g. DNA True or false?

Answer 34

True - can lead to mutation or cancer

Question 35

What are the pharmaceutical drawbacks or irreversible inhibitors?

Answer 35

Their chemical reactivity - leads to them being prone to destruction Their lifetimes are limited by the rate of protein turnover for the target enzyme

Question 36

What are the advantages of mechanism based inhibitors?

Answer 36

Absolute specificity | High enzyme inhibition efficiency - tight covalent bonds

Question 37

Increasing the concentration of substrate has no effect on suicide inhibitors. True or false?

Answer 37

True - non-competitive irreversible inhibitors

Question 38

What is an example of a suicide inhibitor?

Answer 38

5-fluorouracil

Question 39

What are the pharmaceutical drawbacks of suicide inhibitors?

Answer 39

The inhibitor structure may still bind to other cell components There is a problem if the target enzyme is synthesised in the cell as an active precursor Can cause toxicity due to their high reactivity

Question 40

Penicillin acts on enzymes via a suicide inhibitor mechanism. True or false?

Answer 40

True

Question 41

What drug is a irreversible inhibitor of B-lactamase?

Answer 41

Clavulanic acid

Question 42

Clavulanic acid has good antibacterial activity. True or false?

Answer 42

False

Question 43

Clavulanic acid is used as a guard drug for _______

Answer 43

ampicillin

Question 44

The more stable the transition state, the easier the reaction will be and the more effective the enzyme will be as a catalyst. True or false?

Answer 44

True

Question 45

Transition state inhibitors bind less tightly than drugs that mimic the substrate or product. True or false?

Answer 45

False - bind more tightly

Question 46

Renin inhibitors are examples of ______ _______ inhibitors

Answer 46

transition state

Question 47

Transition state inhibitors are designed to mimic the transition state of an enzyme-catalysed reaction. True or false?

Answer 47

True

Question 48

Transition state inhibitors are chemically stable. True or false?

Answer 48

True