Aspirin, DHFR, 5-FU

• what is an inhibitor?

  A molecule or ion that interacts with a enzyme and alters its stucture to reduce its activity
• what is the importance of enzyme inhibitors?

  regulation of cellular activity
• what are the two main types of inhibitor?

  irreversible, reversible
• What is an irreversible inhibitor?


  Inhibitor binds permanently to enzyme. Usually mimics substrate to bind to catalytic centre,

  Becomes covalently attached to catalytic group during catalysis
• what are the types of reversible inhibitors?

  competitive, non-competitive, uncompetitive
• what type are transition state analogues?

  competitive
• what km value is needed for competitive inhibitors?

  low
• where do non-competitive inhibitors bind to?

  non-active site (allosteric)
• where do uncompetitive bind?

  Binds to enzyme substrate complex
• what type of inhibitors are kinase inhibitors?

  mimic structure of ATP - competitive
• what is the name for aspirin?

  acetylsalicyclic acid
• what class of drugs does aspirin belong?


  NSAIDs (nonsteroidal anti-inflammatory drugs)
• what happens if aspirin didnt have acetyl group?

  would be a competitive inhibtor
• what does aspirin do?

  block prostaglandin synthesis
• what is the difference between Cox1 and Cox2?


  Cox1 - widespread and constitutively expressed

  Cox2- released during inflammatory response
• which isoform of Cyclooxygenase doe aspirin inhibit?

  both cox1 and cox2
• where does aspirin bind to?


  Directly to active site and competes with arachindonate
• which hydroxyl group is acetylated by donation by aspirin?


  ser530
• how does aspirin prevent blood clots?

  inhibits COX1 in blood platelates
• How does cox1 reduce blood clotting?

  reduces prostaglandin production
• what does a normal dose of aspirin do?

  anti-inflammatory and pain killer
• what does low dose of aspirin lead to?

  prevention of thrombosis
• what are the side effects of aspirin?

  stomach ulcers
• what is an example of prodrug?


  5-fluorouracil (5-FU)
• what does 5-FU do?


  blocks DNA synthesis by inhibiting the production of pyrimidine bases
• what is 5-FU precursor for?

  irreversible inhibitor thymidylate synthase
• can you do a michaelis-menten plot on irreversible inhibitor?

  no, as the enzyme is taken out of commission
• how can competitive inhibition be over come?

  by adding more substrate
• what is the potency of inhibitor related to?

  The affinity for active site compared to substrate
• what type of inhibitor is methotrexate?

  Competitive
• what is low folic acid acid associated with?

  leukaemia remission
• what does folate play a role in?

  DNA synthesis
• what is Dihydrofolate reductase?

  Involved in the ultilisation of folate for DNA synthesis
• what is methotrexate used for?

  chemotherapy
• what DHFR effective to?

  all rapidly divding cells
• what is methotrexate competiting with?

  DHFR
• what does the deviation from dihydrofolate mean for methotrexate?

  increases affinity
• how to tell a competitive inhibitor?


  Eventually same Vmax
• what happens to Km with competitive inhibition?

  Increases, worse binder to active site
• what does a non-competitive inhibitor mean?

  Active sites are no longer able to catalyse conversion of S to P but S can still bind