The author replies to Ault.
I agree that presentation of the double reciprocal forms and examination of the terms in equations add to an appreciation of enzyme inhibition--once you already understand the topic. The point of my article is that most people don't. Those who specialize in kinetics may feel the need to keep the flame of orthodox kinetics alive by stressing precision in definition, and naturally gravitate toward double reciprocal plots and the behavior evident in equations. The idea that an intuition can be developed through these practices is another matter. Personally, I favor mental pictures such as the sting operation for uncompetitive inhibition. I disagree that we needn't discuss ideal cases of mixed inhibition where both binding constants are equal on the grounds that they are only occasionally observed: what we are talking about is the concept. Unless the extreme cases of the types of inhibition are clearly understood, we will remain ignorant of the central ideas. Even if the extreme case had an occurrence of zero, it would still be worthy of study. Students, professors, and even textbooks currently struggle with the notion of an uncompetitive inhibitor and therefore of any type of inhibition apart from competitive. I don't believe data transformations or deep examination of equations themselves will lead us out of the morass. I am not advocating ignoring more elaborate treatments: I am merely suggesting that, as a first step, a basic understanding is more important than detail.
One final point must be stressed. To retain the emphasis on Km itself rather than V/K is the wrong step, even if we are looking to more advanced treatments. This is because Km is not really a fundamental kinetic constant. Thus, its use, while a simplification and sometimes a useful benchmark, is not a way to more deeply understand kinetics. For a more advanced treatment than my own, I strongly suggest the reader look into Northrop's discussion (1).
Literature Cited
- Northrop, D. B. J. Chem. Educ. 1998, 75, 1153-1157.
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