Enzymes as drug targets Flashcards
What is Vmax?
The maximum rate at which an enzyme
can carry out a reaction
What is Km?
Substrate concentration at which the
enzyme will work at ½ Vmax
What is 1/Vmax?
Where lineweaver burk plot crosses the y axis
What is -1/Km?
Where lineweaver burk plot crosses x axis
What are DD transpeptides?
Also known as penicillin binding protein (PBP)
Carries out crosslinking of peptidoglycan wall subunits for bacteria
How do beta lactams effect DD transpeptides?
Beta lactam antibiotics bind to and irreversibly inhibit DD Transpeptidase
preventing building of new cell walls
How are Beta lactamases responsible for some forms of antibiotic resistance
Bacteria counter the impact of beta lactam drugs by
producing an enzymatic defence system
What do HIV proteases do?
Activity central to HIV replication
Processes (cleaves) viral virion proteins
required for formation of active virus
What is atazanir?
a HIV protease
What are NSAIDs?
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
What is cyclo-oxygenase?
- Responsible for the synthesis of prostaglandins
- These are involved in inflammatory response
- COX inhibitors reduce the synthesis of prostaglandins by inhibiting COX enzymes
What is COX-1?
Constitutive enzyme
Expressed in most tissue
‘housekeeping’ role
production of prostaglandins
What is COX-2?
Inducible enzyme
Production of mediators of inflammation
What COX does asparin inhibit?
COX 1 and 2
What COX does ibuprofen inhibit?
COX1 and 2
What COX does Celecoxib inhibit?
selectively inhibits COX 2
What effects do cylco-pxygenase inhibitors have?
Anti-inflammatory, antipyretic and analgesic effects
What does inhibiting COX enzymes result in?
inhibit the production of prostaglandin
How do COX 2 selective drugs compare to regular cyclo-oxygenase inhibitors?
Lower GI toxicity
What does Angiotensin converting enzyme do?
• 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
Difference between Angiotensin I and II?
- Angiotensin I is inactive, but is converted by ACE to Angiotensin II
- Angiotensin II is a potent vasoconstrictor
Is the order of molecules between Angiotensinogen and the inactive degradation products of Angiotensin III?
Angiotensinogen
Angiotensin I
Angiotenisin II
Angiotensin III
Inactive degradation products
What enzyme cleaves angiotensinogen to Angiotensin I?
Renin
What enzyme cleaves angiotensin I to angiotensin II?
Angiotensin Converting Enzyme
What enzyme cleaves angiotensin II to angiotensin III?
Aminopeptidase
What enzyme converts angiotensin III to the inactive degradation products?
Angiotensinases
How many amino acids constitutes angiotensinogen?
400+
What does angiotensin II do?
potent vasoconstrictor
How does ramipril lower blood pressure?
By inhibiting the proteolytic activity of ACE,
Ramipril decreases the production of
Angiotensin II, decreasing fluid retention
and thereby resulting in lowered blood
pressure
What do protein kinases do?
- 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
What is the function of reverse transcriptase in retroviruses?
It uses viral RNA as a template for DNA synthesis
Drugs developed to treat AIDS are known as reverse transcriptase inhibitors. They worked because they ___.
bonded to the viral reverse transcriptase enzyme, thus preventing the virus from making a DNA copy of its RNA genome.
Fill in the blanks: Angiotensin II causes ___________ of the vessels and triggers the release of ____________.
vasoconstriction; aldosterone
What does a protein kinase do?
it transfers phosphates from ATP to proteins
