Enzymes as drug targets

Question 1

What is Vmax?

Answer 1

The maximum rate at which an enzyme

can carry out a reaction

Question 2

What is Km?

Answer 2

Substrate concentration at which the

enzyme will work at ½ Vmax

Question 3

What is 1/Vmax?

Answer 3

Where lineweaver burk plot crosses the y axis

Question 4

What is -1/Km?

Answer 4

Where lineweaver burk plot crosses x axis

Question 5

What are DD transpeptides?

Answer 5

Also known as penicillin binding protein (PBP)

Carries out crosslinking of peptidoglycan wall subunits for bacteria

Question 6

How do beta lactams effect DD transpeptides?

Answer 6

Beta lactam antibiotics bind to and irreversibly inhibit DD Transpeptidase

preventing building of new cell walls

Question 7

How are Beta lactamases responsible for some forms of antibiotic resistance

Answer 7

Bacteria counter the impact of beta lactam drugs by

producing an enzymatic defence system

Question 8

What do HIV proteases do?

Answer 8

Activity central to HIV replication

Processes (cleaves) viral virion proteins
required for formation of active virus

Question 9

What is atazanir?

Answer 9

a HIV protease

Question 10

What are NSAIDs?

Answer 10

Cyclo-oxygenase inhibitors (one of the more selective coxibs)

NSAIDs are among the most widely used of all medicines. There are now more than 50 different examples on the global market.

• Provide symptomatic relief from fever, pain and swelling in chronic joint disease, as well as in more acute inflammatory conditions
• Inhibits the fatty acid cyclo-oxygenase (COX) enzyme

Question 11

What is cyclo-oxygenase?

Answer 11

• Responsible for the synthesis of prostaglandins
• These are involved in inflammatory response
• COX inhibitors reduce the synthesis of prostaglandins by inhibiting COX enzymes

Question 12

What is COX-1?

Answer 12

Constitutive enzyme
Expressed in most tissue
‘housekeeping’ role
production of prostaglandins

Question 13

What is COX-2?

Answer 13

Inducible enzyme

Production of mediators of inflammation

Question 14

What COX does asparin inhibit?

Answer 14

COX 1 and 2

Question 15

What COX does ibuprofen inhibit?

Answer 15

COX1 and 2

Question 16

What COX does Celecoxib inhibit?

Answer 16

selectively inhibits COX 2

Question 17

What effects do cylco-pxygenase inhibitors have?

Answer 17

Anti-inflammatory, antipyretic and analgesic effects

Question 18

What does inhibiting COX enzymes result in?

Answer 18

inhibit the production of prostaglandin

Question 19

How do COX 2 selective drugs compare to regular cyclo-oxygenase inhibitors?

Answer 19

Lower GI toxicity

Question 20

What does Angiotensin converting enzyme do?

Answer 20

• Angiotensin converting enzyme (ACE) is involved
in regulating the function of the kidney

• Acts as a protease, cleaving angiotensin I and
converting it into angiotensin II, the active form of
the peptide

• This has a number of downstream consequences,
one of which is to increase water retention

Question 21

Difference between Angiotensin I and II?

Answer 21

• Angiotensin I is inactive, but is converted by ACE to Angiotensin II
• Angiotensin II is a potent vasoconstrictor

Question 22

Is the order of molecules between Angiotensinogen and the inactive degradation products of Angiotensin III?

Answer 22

Angiotensinogen

Angiotensin I

Angiotenisin II

Angiotensin III

Inactive degradation products

Question 23

What enzyme cleaves angiotensinogen to Angiotensin I?

Answer 23

Renin

Question 24

What enzyme cleaves angiotensin I to angiotensin II?

Answer 24

Angiotensin Converting Enzyme

Question 25

What enzyme cleaves angiotensin II to angiotensin III?

Answer 25

Aminopeptidase

Question 26

What enzyme converts angiotensin III to the inactive degradation products?

Answer 26

Angiotensinases

Question 27

How many amino acids constitutes angiotensinogen?

Answer 27

400+

Question 28

What does angiotensin II do?

Answer 28

potent vasoconstrictor

Question 29

How does ramipril lower blood pressure?

Answer 29

By inhibiting the proteolytic activity of ACE, Ramipril decreases the production of Angiotensin II, decreasing fluid retention and thereby resulting in lowered blood pressure

Question 30

What do protein kinases do?

Answer 30

* Kinases are enzymes that form an integral part of signaling cascades within the cell * They hydrolyse ATP, transferring the gamma phosphate onto other molecules (often, but not always, other proteins) • Covalent modification with phosphate groups modifies protein function

Question 31

What is the function of reverse transcriptase in retroviruses?

Answer 31

It uses viral RNA as a template for DNA synthesis

Question 32

Drugs developed to treat AIDS are known as reverse transcriptase inhibitors. They worked because they ___.

Answer 32

bonded to the viral reverse transcriptase enzyme, thus preventing the virus from making a DNA copy of its RNA genome.

Question 33

Fill in the blanks: Angiotensin II causes ___________ of the vessels and triggers the release of ____________.

Answer 33

vasoconstriction; aldosterone

Question 34

What does a protein kinase do?

Answer 34

it transfers phosphates from ATP to proteins