Enzyme inhibitors Flashcards
Irreversible inhibitors act at the active site of an enzyme only. True or false?
False - at active site or remote from it
An excess of substrate can displace irreversible inhibitors. True or false?
False
Cephalosporins are examples of reversible inhibitors. True or false?
False - irreversible
Proton pump inhibitors are irreversible inhibitors. True or false?
True
Is orlistat a reversible or irreversible inhibitor?
Irreversible
Reversible inhibitors bind by intermolecular interactions rather than covalent bonds. True or false?
True
Increasing substrate concentration reverses inhibition of reversible inhibitors. True or false?
True
Are anti-depressants reversible or irreversible enzyme inhibitors?
Reversible
Are ACE inhibitors reversible or irreversible enzyme inhibitors?
Reversible
Are statins reversible or irreversible enzyme inhibitors?
Reversible
Competitive inhibitors are usually reversible under what circumstance?
If the concentration of substrate is sufficient enough to displace the inhibitor
For competitive inhibitors, the inhibition depends on three things. What are they?
The concentration of inhibitor
The concentration of the substrate
The relative affinities of the substrate and inhibitor for the active site of the enzyme
A non-competitive inhibitor inhibits at the active site of the enzyme. True or false?
False - adjacent to or distant from the active site
Are non-competitive inhibitors influenced by substrate concentration?
No
What is Kcat?
Overall rate constant for the decomposition of ES complex into products
Substrate analogues and product mimics are ______ ______ inhibitors
ground state
Suicide inhibitors and transition state analogues are _______ ______ inhibitors
mechanism based
Methotrexate is a competitive reversible inhibitor. True or false?
True
Methotrexate has a higher affinity for DHFR than FH2 does. True or false?
True - due to the additional hydrogen and ionic bonds in methotrexate
How does methotrexate work in cancer therapy?
It is a competitive reversible inhibitor and so binds to DHFR stopping the pathway to production of N5,N10-methylene-FH4 and so this means there is no source of methyl for production of dTMP = no DNA synthesis and therefore no cell division
Methotrexate has a similar structure to FH2. True or false?
True
In product mimicking - the final product of the pathway controls the enzyme with the allosteric site. True or false?
True
Anti-purine is a product mimic. How does it work as an anti-cancer drug?
It is an analogue of the final product in purine biosynthesis. It is an allosteric inhibitor of an early enzyme in purine biosynthesis
6-Mercaptopurine is a prodrug. How does it work as an anti-cancer drug?
It is converted into its corresponding nucleoside mono-phosphate and inhibits the first enzyme in the biosynthesis of purine
Product analogues are reversible competitive inhibitors True or false?
False - reversible non-competitive
Which three amino acids posses nucleophilic residues that can be attacked by an electrophilic drug to form a covalent bond in irreversible non-competitive inhibition?
Cysteine
Serine
Histidine
What are the three types of irreversible inhibitors?
Suicide inhibitors
Affinity labels
Group-specific reagents
What are group specific reagents?
React with specific AA side chains
What are affinity labels?
Reactive substrate analogues
Structurally similar to substrate
Capable of covalently binding to active site
Affinity labels are more specific than group specific reagents. True or false?
True
Which drug is an irreversible inhibitor or pancreatic lipase?
Orlistat
Irreversible inhibitors are highly reactive. True or false?
True
The high reactivity of irreversible inhibitors means they can be hydrolysed and so destroyed by nucleophiles such as GSH. True or false?
True
The high reactivity or irreversible inhibitors means that they are likely to be destroyed by attacking other cellular components e.g. DNA True or false?
True - can lead to mutation or cancer
What are the pharmaceutical drawbacks or irreversible inhibitors?
Their chemical reactivity - leads to them being prone to destruction
Their lifetimes are limited by the rate of protein turnover for the target enzyme
What are the advantages of mechanism based inhibitors?
Absolute specificity
High enzyme inhibition efficiency - tight covalent bonds
Increasing the concentration of substrate has no effect on suicide inhibitors. True or false?
True - non-competitive irreversible inhibitors
What is an example of a suicide inhibitor?
5-fluorouracil
What are the pharmaceutical drawbacks of suicide inhibitors?
The inhibitor structure may still bind to other cell components
There is a problem if the target enzyme is synthesised in the cell as an active precursor
Can cause toxicity due to their high reactivity
Penicillin acts on enzymes via a suicide inhibitor mechanism. True or false?
True
What drug is a irreversible inhibitor of B-lactamase?
Clavulanic acid
Clavulanic acid has good antibacterial activity. True or false?
False
Clavulanic acid is used as a guard drug for _______
ampicillin
The more stable the transition state, the easier the reaction will be and the more effective the enzyme will be as a catalyst. True or false?
True
Transition state inhibitors bind less tightly than drugs that mimic the substrate or product. True or false?
False - bind more tightly
Renin inhibitors are examples of ______ _______ inhibitors
transition state
Transition state inhibitors are designed to mimic the transition state of an enzyme-catalysed reaction. True or false?
True
Transition state inhibitors are chemically stable. True or false?
True
