Enzymes as a drug target Flashcards
List 6 factors that impact enzyme activity
pH Temperature regulatory molecules Co-factors Compartmentalisation Feedback inhibition
How do regulatory molecules impact enzyme activity?
Can turn enzymes up or down
How do co-factors impact enzyme activity?
Some enzymes are only active when bond to co-factors
How does compartmentalisation impact enzyme activity?
Storing enzymes in specific compartments can provide the right conditions for activity
How can feedback inhibitors impact enzyme activity?
Enzymes are inhibited by the end product of the pathway they control
What are activators?
Increase enzyme activity
What are inhibitors?
Decrease enzyme activity
What is reversible inhibition?
The binding is reversible
What is a competitive inhibitor?
Inhibitor binds and blocks binding site of substrate
Will decrease rate of reaction when not much substrate but can be out-competed by increasing substrate concentration (can reach maximum rate)
What is a non-competitive inhibitor?
Inhibitor binds to allosteric site
Never reach maximum rate - the enzymes are ‘poisoned’ and can’t do job
What is allosteric regulation?
Regulatory molecule binds to allosteric site
Most non-competitive inhibitors
When binds to enzyme, all active sites on protein subunits are changed slightly
What are allosteric enzymes?
Enzymes that are allosterically regulated with unique properties, typically have multiple active sites
What are allosteric activators?
Bind to locations other than active site, causing increase in function of active site
What is cooperactivity?
Substrate serves as allosteric activator - when it binds to one active site, the activity of the other increases
Characteristics of co-factors
Help enzymes for optimally
Can be temporarily attached by hydrogen/ionic bonds
Can be permanently attached by ionic bonds
What are co-enzymes?
Subset of co-factors that are carbon based
e.g. dietary vitamind
What is compartmentalisation?
Stored in specific part of cell so enzymes are kept where they’re needed and can find substrates readily, as well as maintaining an optimum microenvironment
What is feedback inhibition?
The end product of a metabolic pathway acts on the key enzyme to prevent more of the end product from being produced
Means that the existing supply is used up rather than making excess of the end product
Typically acts as first committed step (irreversible step)
Can act at multiple points along pathway
Example of feedback inhibition using ATP
ATP is allosteric inhibitor of enzymes involved in respiration
Lots of ATP = feedback inhibition = no new ATP
ATP is unstable so will be broken down quickly
ADP = allosteric activator for enzymes inhibited by ATP
When ADP>ATP, respiration enzymes are active and make more ATP
Symptoms of myasthenia gravis
Fatiguability and becomes weaker
How can you treat myasthenia gravis?
Thymectomy
Steroids
Immunosuppressants
Pyridostigmine
What does pyridostigmine do?
Prevents breakdown of acetylcholine
What are regulatory molecules?
Activation and competitive vs non-competitive inhibitors, allosteric binding, induces conformational change
What are co-factors and co-enzymes?
Additional molecules, co-factors are inorganic and co-enzymes are organic (e.g. magnesium or iron)
What is compartmentalisation?
Enzymes stored in place with specific environment and they can’t function outside this environment (e.g. stomach enzymes and pH)
What is feedback inhibition?
The end product of a pathway inhibits an earlier stage of the same pathway (e.g. ADP and ATP)
What is a kinase molecule?
Catalyses transfer of phosphate from high-energy, phosphate-donating molecules to specific substrates via phosphorylation
What is a dehydrogenase molecule?
Removes/transfers hydrogen from a substrate
What is a phosphatase molecule?
Uses water to cleave phosphoric acid monoester into phosphate ion and alcohol
What is a synthase molecule?
Catalyses synthesis of two molecules
What is a protease molecule?
Catalyses proteolysis by cleaving peptide bonds between peptides by hydrolysis
What is a lipase molecule?
Catalyses breakdown of lipids by hydrolysis
What is IC50?
Half maximal inhibitory concentration (measures how potent an inhibitory molecule is). Measures how much of an inhibitor is needed to reduce the activity of an enzyme by 50%
What does SOCRATES stand for when doing a consultation?
- Site
- Origin
- Characteristics
- Radiation of pain
- Associated symptoms
- Timing of pain
- Exacerbating factors
- Severity of pain
What doe NSAIDs do?
Inhibit the cyclooxygenase enzymes
What does COX 2 do?
Creates prostaglandins that lead to inflammation
What does COX 1 do?
Normal physiological function
Why do NSAIDs normally cause a lot of side-effects?
The drugs are non-specific and so wear down stomach lining
What are the four enzymes that act on arachidonic acid?
Cyclooxygenase, phospholipase, 5-lipoxygenase, 12-lipoxygenase
