Pharmacology: Enzymes Flashcards
How would you represent Michaelis-Menten kinetics mathematically?
V= Vmax [S] / Km + [S]
What does Vmax imply?
The enzymes are saturated and the rate of production of the reaction product is occurring at the maximum possible rate.
In Michaelis-Menten kinetics, how do you increase Vmax?
By adding more enzyme to the system
How is the Michaelis constant derived?
Km has the same unit as [S], and at a certain point on the graph, Km = [S]. Therefore, V = Vmax [S]/ Km + [S], V = Vmax [S]/ [S] + [S], V = Vmax [S] /2[S]. V = Vmax /2 when Km = [S]. Therefore, the Km is always half the Vmax.
What is the practical implication of the Michaelis constant in pharmacology?
Affinity of an enzyme for a substrate- Where the Km is low, the enzyme has a high affinity for the substrate. I.e., for a given concentration of enzyme and substrate, maximal production of the reaction product is achieved at lower concentrations of the substrate, and vice versa.
What is the Lineweaver Burk plot?
A linear graphical representation of Michaelis-Menton kinetics where 1/V is plotted on the Y-axis and 1/S is plotted on the X axis. Where the line intersects with the Y axis, this represents 1/Vm, and where the line intersects with the X axis, this represents -1/Km.
What is the effect of competitive inhibitors on Michaelis-Menton kinetics?
They increase the Km without having any effect on the Vmax. In real terms, more substrate is required to overcome the inhibitory effect of the competitive inhibitor.
What is the effect of non-competitive inhibitors on Michaelis-Menton kinetics?
They decrease the Vmax without having any significant effect on Km. In real terms, they take enzymes out of commission, so that they only rectifying action to increase the Vmax is to add more enzyme.
What is the effect of competitive inhibitors on the slope of the line on a Lineweaver-Burk plot?
Competitive inhibitors increase the slope of the Km/Vm line
What is the effect of non-competitive inhibitors on the slope of the line on a Lineweaver-Burk plot?
Non-competitive inhibitors increase the slope of the Km/Vm line
What is the difference between potency and efficacy?
Potency is the amount of a drug required to deliver a desired response, whereas efficacy is the maximal effect a drug can produce.
What is the difference between graded and quantal efficacy?
Graded efficacy is where the response can only be measured on a scale, i.e. 0-10 pain scale, a quantal response is where the response is considered in binary or ‘yes/no’ terms, i.e. achieved BP <130/<80, did not achieve BP <130/<80.
What is the effect of a competitive antagonist on the ED50 and the Emax?
It will have no effect on the Emax, in that the maximal response can still be achieved but at higher doses than would be needed in the system otherwise.
What is the effect of a non-competitive antagonist on the ED50 and the Emax?
A non-competitive inhibitor causes a reduction in the Emax without any impact on the ED50 of the drug.
What drugs have a low therapeutic index?
Lithium, warfarin, digoxin, and theophylline.
