Enzyme - Inhibition Flashcards
Irreversible Inhibition
Is the permanent binding of an inhibitor to an enzyme, typically mimicking substrate binding catalytic centre.
What is an example of Irreversible Inhibition?
Acetylsalicyclic Acid
5-Fluorouracul
Acetylsalicyclic Acid
This is a nonsteroidal anti-inflammatory drug- reducing signs of inflammation.
What does ASA target/inhibit?
Cyclocoxygenase
Cyclooxygenase
These are enzymes producing prostaglandins, prostacyclinc and thromboxane converting arachidonic acid to prostaglandin H2
What are the two isoforms of Cycloxygenase?
COX-1
COX-2
COX-1
This maintains physiological functions like aggregation of platelets being widepsred expressed
COX-2
This produces prostaglandins contributing to inflammation, pain and fever induced by inflammatory stimuli
What is the mechanism of action for aspirin?
Acetylation nuclephilic attack of Ser-530 hydroxyl gene of the active sites meaning arachidonic acid can no longer bind, inhibiting prostaglandin and thromboxanes production
What properties does aspirin have?
Analgesic and Antipyretic occuring by prostaglandin synthesis inhibition and hypothalamus action
Analgesic
These are medications used in managment and treatment of pain
Antipyretic
These are fever-reducing dtugs
How does aspirin inhibit?
Acetyl side group is transferred to the serine residue inhibiting the enzyme permanently despite the competition
Arachidonic Acid
This is a polyunsaturated FA being excised from the membrane by phospholipase A2 to act as a substrate
What can aspirin be used for?
Prevention of blood clots, which increases heart attack incidence of aspiring are used in tandem with cholesterol reducing agents like statins
How may AA apromote platelet aggregation?
Thromboxane A2 when synthesised and produced from AA by COX-1 in platelets
5 Fluorouracil
This is a chemotherapy drug inhibiting DNA synthesis by prevetion of pyrimidine base production
Thymidylate Synthase
This is an enzyme catalysing deoxyuridine monophosphate to deoxythymidine monophosphate
What happens in the catalysis of 5-FLuorouracil
5-FU is converted to dUMP by TS which inhibits TS, otherwise catalysing dUMP conversion to dTMP being a precursor for thyrmidylate.
Why is it hard to describe irreverisble inhibition by MMK?
MMK relies on equilibrium below where active enzyme concentration is contanst
Reversible Inhibition
This has three categories: competitive, non-competitive or uncompetitive.
What does competitive inhibition require?
An inhibitor with low kM so it can bind more effectively than substrate
Competitive Inhibition
These are substances combining to the active site of the enzyme being similar in structure to the subrate
Methotexate
This is a chemotherapy drug used to treat cancers like leukemia inhibiting Dihydrogolate Reductase required for DNA synthesis
What is an example of Competitive Inhibition?
Methotrexate resembling dihydrofolate
How does methotrextate competitively inhbiiti Dihydrofolate Reductase?
Competes for hydrogen bond formation within the active site with a higher affinity for the reductase than hydrogolate
How can Comp inhibition be represented in an MM graph?
Vmax remains unchanged due to if you add another substrate the inhibition can be outcompeted
How does kM increase in competitive inhibition?
Proportional to inhibitory as more the inhibition you have the lower the affinity of the substrate
Lineweaver-Burk Plot
This is a graphical representation of the MMK equation
Non-Competitive Inhibition
This binds at an allosteric site seperate form the active site of substrate binding, thus regardless of presence of bound substrate
What is Vmax in Non-comp Inhibition?
Vmax is reduced, as enzyme cannot reach full velocity because regardless of amount of substrate added the inhibitory cannot be outcompeted
What is Km in non-comp inhibition?
Remains unchanged due to fact the affinity of the active site has not changed, only ability to convert the substrate to product
Mixed Non-Competitive Inhibition
Affects both substrate binding site and catalysis, so Vmax decrease and Km increase
Uncompetitive Inhibition
These bind only to ES compelx not the free enyme
What happens in uncompetitive inhibition?
Inhibitor binds to ES and not E
What is an example of Uncompetitive Inhibition?
Lithium as a drug treatment for manic depression, inhibiting myo-inositol monophosphatase
Whta happens to Vmax in Uncomeptitive Inhibition?
Decrease because substrate is frozen, blocking others getting in as well as cannot be converted to product
What happens to Km in Uncompetitive Inhibtion?
Decrease because substrate locked so affinity of the enzyme has increased.
