Lecture 9 Flashcards
(38 cards)
What is an inhibitor?
A molecule or ion that reduces the activity of an enzyme.
3 uses of enzyme inhibitors?
Regulation of cellular activity,
many common drugs and toxins are enzyme inhibitors,
can be used to investigate enzyme mechanisms.
What 2 main types of inhibitor exist?
Irreversible and reversible inhibitors.
3 types of reversible inhibitors, and where they act?
Competitive, active site.
Non-competitive, non-active site.
Uncompetitive, binds ES complex.
What happens in irreversible binding?
Inhibitor binds covalently (or by very high affinity non-covalent binding) to the enzyme permanently, usually at the active site, inactivating it.
Is irreversible binding toxic, and does it inhibit suicide?
Yes, typically to cells.
Yes.
Where can aspirin be found?
White willow bark,
Meadowsweet.
When was Aspirin first marketed?
1899.
What class of drug is aspirin?
NSAID (nonsteroidal anti-inflammatory drug).
What do NSAIDs do?
Block prostaglandin synthesis pathway.
How is Prostaglandin H2 synthesised from Arachidonate?
Arachidonate converted to Prostaglandin G2 by cyclooxygenase.
Prostaglandin converted to Prostaglandin H2 by Peroxidase.
How many isoforms of cyclooxygenase exist, and where/when are they found?
2 types. COX1 and COX2.
COX1 - widespread and constitutive.
COX2 - released during inflammatory response.
What benefit is conferred to COX by a hydrophobic channel down the enzyme’s middle?
Enables arachidonate fatty acid to bind.
How does Aspirin affect COX?
It blocks the hydrophobic channel, preventing substrates from entering and binding.
What is the chemical name for aspirin?
Acetylsalicylate.
Which 3 other molecules also act as COX inhibitors, bar aspirin?
Why do they work?
Acetaminophen (Paracetamol)
Ibuprofen
Naproxen.
All share a similar structure.
What is a pharmacological application of a low dose of aspirin?
How does it work?
Prevents thrombosis.
Inhibits COX1 in blood platelets, prevents prostaglandin/thromboxane-mediated aggregation.
What is a pharmacological application of a normal dose of aspirin?
How does it work?
Anti-inflammatory and pain killer.
Inhibits COX1 and COX2 in most tissues, reducing inflammation, pain responses and fever.
What is a side effect of aspirin, and why?
Stomach ulcers.
Prostaglandins prevent acid secretion (COX1).
What can the enzyme bind in competitive inhibition?
Enzyme can bind either substrate or inhibitor.
How can inhibition be overcome in competitive inhibition?
Addition of more substrate.
What is the potency of inhibitor related to?
Affinity for active site compared to substrate.
What was discovered in 1948 to be associated with leukaemia remission?
Low folic acid diet.
Why is DHFR important?
Key enzyme in folate metabolism. First target for chemotherapy drugs.
