LETTER pubs.acs.org/jchemeduc
About the Soundness of Assuming a “Rate-Limiting Step” in the MichaelisMenten Model Juan C. Aledo,*,† Susana Jimenez-Riveres,† and Manuel Tena Aldave‡ † ‡
Departamento de Biologia Molecular y Bioquimica, Facultad de Ciencias, Universidad de Malaga, 29071 Malaga, Spain Departamento de Bioquimica y Biologia Molecular, Edificio Severo Ochoa, Campus de Rabanales, Universidad de Cordoba, 14071 Cordoba, Spain ABSTRACT: This is a response to Sidney Toby’s letter (DOI: 10.1021/ed100288j) about the article “The Effect of Temperature on the Enzyme-Catalyzed Reaction: Insights from Thermodynamics” (DOI: 10.1021/ed800088n). KEYWORDS: Upper-Division Undergraduate, Biochemistry, Misconceptions/Discrepant Events, Enzymes, Kinetics, Rate Law, Thermodynamics
n his comment1 relating to our article, “The Effect of Temperature on the Enzyme-Catalyzed Reaction: Insights from Thermodynamics”,2 Sidney Toby points out some caveats regarding the use of the concept “rate-limiting step”. More concretely, he stresses the risk of assuming that the slowest elementary step of a mechanism determines the reaction rate. Thus, this author claims the convenience of computer simulations to describe the kinetic behavior of complex reaction mechanisms. In a general context, we would not object to this claim. However, when deriving the MichaelisMenten equation from a mechanism involving two sequential elementary steps,
I
k1
k2
E þ S a ES sf E þ P k1
under well-defined conditions (k2 , k1, k1 and [E] , [S]), then, the application of the concept of rate-limiting step, that is, that the rate of the enzyme-catalyzed reaction is determined by the rate of the second elementary step ½S v ¼ k2 ½ES ¼ Vmax KM þ ½S is not only a sound praxis, but it is a very convenient one, mainly because of its unbeatable simplicity in a teaching context. In any case, that is the way that most textbooks use to derive the MichaelisMenten equation from this basic model. We think that the soundness of such an approach is beyond doubt. Thus, the discussion could be focused on whether there is a more convenient alternative, for teaching purposes, to the current approach. If that turns out to be the case, we will welcome it.
’ AUTHOR INFORMATION Corresponding Author
*E-mail:
[email protected].
’ REFERENCES (1) Toby, S. J. Chem. Educ. 2011, 88; DOI: 10.1021/ed100288j. (2) Aledo, J. C.; Jiminez-Riveres, S.; Tena, M. J. Chem. Educ. 2010, 87, 296–298. Copyright r 2011 American Chemical Society and Division of Chemical Education, Inc.
Published: June 10, 2011 1029
dx.doi.org/10.1021/ed101181b | J. Chem. Educ. 2011, 88, 1029–1029