Enzymes as drug targets Flashcards
(22 cards)
What are enzymes?
- Enzymes are specialised protein binding sites that are specific for certain substrates
- Once bound, substrate is modified
- Binding pocket is the active site
Explain the kinetics behind enzymes?
Enzymes are catalysts that alter the activation energy of a particular reaction
What is the Vmax?
The maximum rate at which an enzyme can carry out a reaction
What is the Km?
Substrate concentration at which the enzyme will work at 1/2 Vmax
How do you plot the graph of an enzyme?
Reaction rate against the substrate concentration
How does a reaction occur in an enzyme?
- Substrate enters enzymes activate site
- Enzyme binded substate
- Enzyme releases product
How does competitive inhibition work in an enzyme?
- Inhibitor attaches to the active site (shares steric properties)
- Prevents the substrate binding and competes with the substrate
What does the Ki constant represent?
Ki is the constant that describes how frequently the inhibitor binds to the enzyme or the enzyme substrate
What is the line weaver burke plot?
- Plots the 1/v (velocity) and the 1/s (substrate concentration)
- Allows you to work out Vmax and Km easily
How are enzymes used as drug targets for infectious agents?
- Enzymes produced by infectious agents can be switched off- fatal for bacteria or virus
- Bactericidal drugs target enzymes produced by humans
- Viral enzymes can be targeted to prevent viral replication
Give an example of a class of drugs used against bacteria? And describe how it works?
- Penicillin (Penicillin binding protein) aka DD transpeptidases
- Carries out cross linking of peptidoglycan wall subunits for bacteria
- Beta lactam antibiotics bind to and irreversibly inhibit the DD transpeptidases that help rebuild the peptidoglycan wall
How do bacteria counter beta lactam drugs?
- Contain a protein and enzyme called bata lactamases for bacteria resistance
- Can be transferred from viruses to viruses
Describe how HIV protease works?
Central to HIV replication as it processes and cleaves viral virion proteins required for formation of active virus
Explain how atazanavir works?
- Will prevent the protease from HIV from processing HIV proteins from replicate
- Will reduce amount of circulating virus so reduces immunodeficient response
Why might we want to target and change human enzymes?
- Can change the physiological function of the enzyme through changing protein sequence
- Caused mutations lead to human diseases and altered enzyme function
- Drugs can correct these changes
What is ACE and describe its role?
- ACE= Angiotensin converting enzyme
Involved in regulating the function of the kidney
- Acts as a protease to cleave Angiotensin I and converts it to Angiotensin II (active form of peptide)
- Can cause increase in water retention
Describe how ACE inhibitors work? And give an example?
- Inhibit the activity of ACE which leads to the decrease in the production of Angiotensin II
- This decreases fluid retention and results in lower blood pressure
- Example: Ramipril
Describe how cyclo-oxygenase works?
Synthesises prostaglandins which are involved in the inflammatory response
Describe how COX inhibitors work?
- Reduce the synthesis of prostaglandin by inhibiting the COX enzymes
- So it can reduce the generation of heat and body temperature
Give an example of COX inhibitor?
Ibuprofen and other NSAIDS
Describe how protein kinases work and give an example of where they are used?
- Protein kinases are key regulatory enzymes that regulate a whole range of proteins
through the addition of the phosphate group - Form an integral part of signalling cascades within the cell
- Hydrolyse the ATP, transferring gamma phosphate into other molecules
What is allosteric modulation?
- When the drug can alter the enzymatic function by binding to sites distant fro the actual active site
- Alter overall protein shape (conformation) which can lead to altered substrate binding or active site function
