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ERIC Number: EJ826630
Record Type: Journal
Publication Date: 2009
Pages: 5
Abstractor: As Provided
ISSN: ISSN-1470-8175
A Qualitative Approach to Enzyme Inhibition
Waldrop, Grover L.
Biochemistry and Molecular Biology Education, v37 n1 p11-15 Jan-Feb 2009
Most general biochemistry textbooks present enzyme inhibition by showing how the basic Michaelis-Menten parameters K[subscript m] and V[subscript max] are affected mathematically by a particular type of inhibitor. This approach, while mathematically rigorous, does not lend itself to understanding how inhibition patterns are used to determine the kinetic aspects of an enzyme. The discussion here describes a qualitative approach to teaching enzyme inhibition that allows for a physical or mechanistic understanding. This qualitative approach to enzyme inhibition starts by recognizing that the two fundamental kinetic parameters of an enzyme catalyzed reaction are V[subscript max] and V[subscript max]/K[subscript m], which correspond to the apparent rates of reaction at very high and very low concentrations of substrate, respectively. It just so happens that the reciprocals of V[subscript max] and V[subscript max]/K[subscript m] correspond to the y-intercept and slope of the Lineweaver-Burk plot, respectively. Thus, an inhibitor that affects the y-intercept binds to the enzyme at very high substrate concentrations, and thus binds to the enzyme-substrate complex, while an inhibitor that affects the slope binds to the enzyme at very low substrate concentrations, and thus binds only to free enzyme. These simple precepts can be used to interpret the basic inhibition patterns, competitive, uncompetitive and noncompetitive, and more importantly, derive mechanistic information, especially in multisubstrate reactions. The application of these principles is illustrated by using an example from cancer chemotherapy, the inhibition of thymidylate synthase by 5-fluorouracil and leucovorin. (Contains 5 figures and 4 footnotes.)
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Publication Type: Journal Articles; Reports - Descriptive
Education Level: Higher Education
Audience: N/A
Language: English
Sponsor: N/A
Authoring Institution: N/A