Enzymes & Drug Resistance

Question 1

Clinical Effect of drugs decreased when (2)

Answer 1

1) a natural inbuilt resistance in some individuals and organisms or
2) may arise naturally in the course of treatment.

Question 2

The inbuilt resistance is probably due to

Answer 2

differences in the genetic code of individual organisms within a species

Question 3

Whereas in natural selection, the drug kills the weaker strains of an organism but does not affect other strains of the same organism

Answer 3

other strains of the same organism

Question 4

when the antibiotic is stopped the immune strains multiply and become the ______________, which eventually results in ineffective drug treatment.

Answer 4

common strain of the organism

Question 5

Resistance occurs on an individual basis and so is not usually detected until a

Answer 5

wide sample of the population has been treated with or indirectly exposed to the drug.

Question 6

when do new drugs need to be discovered to treat the condition

Answer 6

When resistance happens

Question 7

drug resistance emergence is thought to be due to the

Answer 7

widespread and poorly controlled use of a drug.

Question 8

For example, the generous use of antibiotics in farming is strongly suspected to be the reason for an increase in

Answer 8

antibiotic-resistant strains of bacteria in humans

Question 9

The way MC have been tackling this resistance is either to (2)

Answer 9

come up with new drugs
or
to modify existing drugs

Question 10

But the problem here with new drugs for drug resistance is that there is a probability of new drugs not working as well as being time consuming and expensive (2)

Answer 10

• new drugs not working

- being time consuming and expensive.

Question 11

it would be better if, in future, we reduced the possibility of resistance by

Answer 11

using the effective existing drugs more intelligently

Question 12

Drug action on Cell Walls/Membranes (4)

Answer 12

1 Inhibiting the action of enzymes and other substances

2 Inhibiting processes involved in the formation of the cell wall

3 Forming channels through the cell wall or membrane

4 Breaking down sections of the membrane

Question 13

Drug resistance can be linked to a change in either the (2)

Answer 13

permeability of the membranes of the organism
or
an enzyme system(s) of the organism.

Question 14

Most drugs act on the (2)

Answer 14

enzymes
and
receptors found in cell membranes and walls

Question 15

A number of drugs act by (3)

Answer 15

1 blocking ion channels,
2 disrupting the structure of the cell membranes and walls
3 inhibiting the formation of cell membranes and walls.

Question 16

Snake example bursting red blood cells of the infected mammal

Answer 16

The venoms of both the eastern diamondback rattlesnake and the Indian cobra contain the enzyme phospholipase A2.
This enzyme catalyses the hydrolysis of the C2 fatty acid residue from phosphatidyl lipids. The phospholipid product of this hydrolysis acts as a detergent, breaking down the membranes of red blood cells and causing them to burst, usually with fatal results to the infected mammal.

Question 17

In general, drugs that act by disrupting the structure of membranes and walls, or their synthesis, appear to act by: (4)

Answer 17

1. inhibiting the action of enzymes and other substances in the cell membrane involved in the production of compounds necessary for maintaining the integrity of the cell;
2. inhibiting processes involved in the formation of the cell wall, resulting in an incomplete cell wall and leading to loss of vital cellular material and subsequent death of the cell;
3. forming channels through the cell wall or membrane, making it more porous and resulting in the loss of vital cellular material and the death of the cell;
4. making the cell more porous by breaking down sections of the membrane.

Question 18

All microorganisms have plasma membranes that have characteristics in common. Consequently, drugs can act by the same mechanism on quite different classes of
microorganism. For example,

Answer 18

griseofulvin is both an antifungal and an antibacterial agent

Question 19

The membranes of prokaryotic cells exhibit a number of

significantly different characteristics to those of

Answer 19

eukaryotic cells

Question 20

The membranes of prokaryotic cells exhibit a number of
significantly different characteristics to those of eukaryotic cells. It is these differences that must be exploited by medicinal chemists if they are to find new drugs

Answer 20

find new drugs to treat microbiological infestations.

Question 21

However, the membranes of prokaryotic cells exhibit a number of
significantly different characteristics to those of eukaryotic cells. They also account for the selectivity of current drug substances

Answer 21

when used on humans, animals and plants.

Question 22

A significant increase or decrease from the normal concentration of an enzyme can result in

Answer 22

resistance to a drug

Question 23

The overproduction of an enzyme can have two effects:

Answer 23

1. The target process catalysed by the enzyme will not be inhibited because excess enzyme is produced. (competition)

An example of this is the resistance of malarial parasites which is believed to be caused by overproduction of dihydrofolate reductase due to the drug stimulating the parasite’s RNA.

2. The increased production of enzymes that inactivate the drug, for example b-lactamases inactivate most penicillins and cephalosporins by hydrolysing their b-lactam rings.

Question 24

ATP is believed to be the usual provider of (2)

Answer 24

phosphate and adenylic acid

Question 25

acetyl coenzyme A is thought to be the normal source of

Answer 25

acetyl groups

Question 26

72 A number of enzymes deactivate inhibitors by incorporating (conjugation) (3):

Answer 26

1 phosphate by phosphorylation of hydroxyl groups

2 adenine by adenylation of hydroxyl groups

3 acetyl by acetylation of amino groups in the inhibitor’s structure.

Question 27

Many _____________ antibiotics are susceptible to this type of enzyme inhibition mentioned in flash card #72 of this deck

Answer 27

aminoglycoside

Question 28

The underproduction of an enzyme could result in insufficient enzyme being present to produce the active form of a drug from a prodrug

Answer 28

enzyme being present to produce the active form of a drug from a prodrug

Question 29

The underproduction of an enzyme could result in insufficient enzyme being present to produce the active form of a drug from a prodrug

Answer 29

enzyme being present to produce the active form of a drug from a prodrug

Question 30

Example of: The underproduction of an enzyme could result in insufficient enzyme being present to produce the active form of a drug from a prodrug.

Answer 30

The resistance to the antileukaemia drug 6-mercaptopurine is caused by a reduced production of an enzyme required to convert the prodrug to its activeribosyl 50-monophosphate derivative.

Question 31

Increased production of the substrate can prevent _____

________ _________ from binding to the _____ _____ in sufficient quantities to be effective.

Answer 31

competitive reversible inhibitors

active site

Question 32

The high concentration of the substrate means it is in a better position to

Answer 32

compete with the inhibitor, and is more likely to ‘win’.

Question 33

#103
The high concentration of the substrate means it is in a better position to

Answer 33

compete with the inhibitor, and is more likely to ‘win’.

Question 34

in relation to flashcard #103
An example of this is the inhibition of dihydropteroate synthetase by sulphonamides which results in a build-up of p-aminobenzoic acid. This increase in substrate concentration prevents sulphonamides from inhibiting dihydropteroate synthetase, which is a key enzyme in the production of the RNA necessary for bacterial reproduction.

Answer 34

p-aminobenzoic acid

Question 35

The increase in substrate concentration prevents sulphonamides from inhibiting _______ _________, which is a key enzyme in the production of the ______ necessary for bacterial reproduction.

Answer 35

dihydropteroate synthetase

RNA

Question 36

In relation to slide #103

Another example is the build-up of _______ which will overcome the effect of _____ inhibitors.

Answer 36

angiotensin I

ACE

Question 37

It is thought to be the reason for the concentration of plasma angiotensin II returning to normal in some cases where there has been

Answer 37

a chronic administration of ACE inhibitors

Question 38

antibiotic trimethoprim structure

Answer 38

see slide

Question 39

Changes in the structure of the target enzyme results in a

Answer 39

structure that is not significantly inhibited by the drug

Question 40

the modified enzyme is still able to produce the normal product of the reaction, which allows

Answer 40

the unwanted metabolic pathway to continue to function

Question 41

the modified enzyme is still able to produce the normal product of the reaction, which allows

Answer 41

the unwanted metabolic pathway to continue to function

Question 42

resistance to the antibiotic trimethoprim is believed to be due to

Answer 42

a plasmid-directed change in the structure of dihydrofolate reductase in the bacteria

Question 43

Alternative Metabolic pathway diagram

Answer 43

see slide

Question 44

The blocking of a metabolic pathway by a drug can result in the

Answer 44

opening of a new pathway controlled by a different enzyme that is not inhibited by the same drug

Question 45

In biochemistry, a metabolic pathway is a linked series of

Answer 45

chemical reactions occurring within a cell

Question 46

The reactants, products, and intermediates of an enzymatic reaction are known as

Answer 46

metabolites

Question 47

metabolites are modified by a

Answer 47

sequence of chemical reactions catalyzed by enzymes

Question 48

In most cases a metabolic pathway, the product of one enzyme acts as the

Answer 48

substrate for the next

Question 49

set products are considered waste and

Answer 49

emoved from the cell

Question 50

These enzymes often require ____ _______, ______ and ______ _____to function

Answer 50

dietary minerals,
vitamins, and
other cofactors

Question 51

ribozymes diagram

Answer 51

see slide

Question 52

Ribozymes are what type of enzymes

Answer 52

ribonucleic acid enzymes

Question 53

Ribozymes are RNA molecules that are capable of

Answer 53

catalyzing specific biochemical reactions, similar to the action of protein enzymes.

Question 54

A number of biological reactions in which certain RNA molecules act as _________ have been discovered

Answer 54

catalysts

Question 55

These catalytic RNAs exhibit many of the same general properties as

Answer 55

protein-based enzymes

Question 56

three characteristics ribozymes exhibit like protein-based enzymes (3)

Answer 56

1 they are substrate specific
2 increase reaction rate and
3 reappear unchanged at the end of the reaction

Question 57

in a number of casesribozymes action appears to be significantly enhanced by the presence of protein subunits

Answer 57

presence of protein subunits.

Question 58

subunits do not act as catalysts for the reaction in the absence

Answer 58

of the ribozyme