ENZYMES IN DISEASES Flashcards
what are enzymes?
biological catalysts
what do enzymes enable?
enable reactions to take place in living material that would otherwise occur only very slowly or only under very harsh conditions
what is the function of enzymes?
speed up the attainment of equilibrium of a reaction without altering the final equilibrium position
are enzymes specific?
yes
why are reactions that enzymes catalyse specific?
because the composition of the active site is characteristic of a single enzyme catalysing a specific reaction
what causes enzymes to be specific?
Only the correct substrate will bind to the active site
The specificity of binding depends on the shape of the substrate and enzyme molecule
do enzymes have a high or low molecular mass?
high
what is the amount of enzyme needed in a reaction?
very small
how is an enzyme recognised?
by its activity, and the initial velocity (v0) of the reaction catalysed is what we can easily measure
define units of enzymes
the amount of enzyme which will catalyse the transformation of
1 μmol of substrate to product in 1 min
what does damage to cells by acute disease lead to?
increases the permeability of the cell memb, so that cytoplasmic enzymes, like lactate dehydrogenase, leak out into the circulation and their activity can be detected in serum
why is the measurement of the amount of lactate dehydrogenase in the serum important?
it is of clinical importance in diagnosis and prognosis
After myocardial infarction does the serum lactate dehydrogenase rise or fall?
rises
what are the factors affecting the rate of an enzyme catalysed reaction?
Enzyme conc Substrate conc pH Temperature Inhibitors Coenzymes, cofactors, prosthetic groups
what is Vmax?
the maximum velocity (rate) of the reaction. It occurs at saturating [S]
what is Km?
the Michaelis constant
It is equal to the substrate conc at which the rate is half of the maximum rate, Vmax.
what is Km a measure of?
affinity of the E for S and is the [S] needed to achieve half Vmax
what have high Km values?
Enzymes with low affinities for their substrate
what have low Km values?
Enzymes with high affinities for their substrate
what does an inhibitor do?
binds to the enzyme and prevents it from being active
what are inactivators?
Very tightly (irreversibly) bound inhibitors they stop the enzyme-catalysed reaction Initial velocity v0 is zero.
what do reversibly bound inhibitors do?
reduce the initial velocity, v0, according to how much of it is bound
what are the 2 types of reversibly-bound inhibitors?
competitive
non-competitive
how do competitive inhibition work?
both the substrate, S, and the inhibitor, I, bind to the same site on the enzyme, the active site
what happens at very high conc of substrate?
they will displace all of the inhibitor from the active site, so there is no inhibition and the Vmax is unchanged from the non-inhibited case
what is the Lineweaver Burk plot?
used to determine the type inhibition caused
give an example of a competitive inhibitor
Methotrexate
what is methotrexate?
an anti-cancer drug. It is a structural analogue of tetrahydrofolate It inhibits the enzyme Tetrahydrofolate Reductase, involved in purine and pyrimidine synthesis
what does non-competitive inhibition involve?
Inhibitor binds at a different site to the substrate.
Inhibitor can bind to E or ES equally well.
in non-competitive inhibition does the binding of S change?
no, but the enzyme can no longer transform the substrate to the product as efficiently
Vmax is decreased
give an example of a non-competitive inhibitor
Deoxycycline
what is Deoxycycline?
inhibitor of the enzyme Collagenase.
It covalently binds to this enzyme.
Collagenase is a bacterial proteolytic enzyme which damages the gums.
Inactivation of this enzyme is used to treat peridontal disease.
what do competitive inhibitors compete with?
compete with the substrate for binding to the active site of the enzyme, reducing the affinity of enzyme for its substrate
how is Vmax effected in competitive inhibitors?
unaltered
how is Km effected in competitive inhibitors?
increased
where do non-competitive inhibitors bind?
at a site distant from the active site, causing a change in shape of the enzyme
reducing its effectiveness at converting substrate to product
how is Vmax effected in non-competitive inhibitors?
reduced
how is Km effected in non-competitive inhibitors?
unaltered
what is irreversible inhibition?
binds irreversibly and forms covalent bonds to AA residues at or near the active site
what does irreversible inhibition do?
alters the shape of the enzyme causing it to lose its biological activity
Permanently inactivates the enzyme
give examples of irreversible inhibitors
penicillin
aspirin
what is penicillin?
covalently binds to the enzyme Transpeptidase, which synthesises cross links in some bacterial cell walls
Inactivating this enzyme prevents the synthesis of new bacterial cell walls so kills off a bacterial infection
what does MRSA stand for?
Methicillin-Resistant Staphylococcus Aureus
what is MRSA?
β-lactam antibiotic
what is aspirin?
covalently binds to Cyclo-oxygenase(COX) enzymes, which add oxygen molecules to unsaturated fatty acids during the synthesises of prostaglandin
