How to learn enzyme inhibition without memorizing facts

Posted by Jacob M. on 2/3/21 12:30 PM

Title_ How to Study Efficiently for Hours On End (With the Help of a Tomato)-Jan-26-2021-08-52-45-81-PMThe MCAT contains LOTS of material that can often feel quite overwhelming. With this mountain before you, it can feel like the best thing to do is to memorize as many facts as possible to simply regurgitate on test day. I’m here to tell you: this isn’t your only option!

When I was studying for the MCAT, I found that rote memorization of material wasn’t helpful for me when trying to efficiently move through problems. Instead, an intuitive understanding of the material was instrumental in my capacity to quickly solve problems. After practicing how to derive facts on my own, I was able to answer problems without depending on memorization.

Let’s use enzyme inhibitor kinetics as an example of how to gain an intuitive understanding of concepts that appear on the MCAT. The MCAT tests you on the effect of inhibitors on enzyme kinetics. For each type of inhibition, you need to know the effect on KM (the Michaelis-Menten constant) and Vmax (the maximum rate of catalysis). Here is the information you need to know regarding enzyme inhibition:

 

Type of inhibition

Effect on KM

Effect on Vmax

Competitive

Increases

Stays the same

Uncompetitive

Decreases

Decreases

Noncompetitive

Stays the same

Decreases

Mixed

Increases or decreases

Decreases

 

You could simply memorize this information, but we’ll go through how to think about it at a more basic level to avoid that memorization.

First, a review of the different types of inhibition. When an enzyme binds with a substrate, there are three different states:

  1. Enzyme and substrate are separate
  2. Enzyme and substrate are bound together
  3. Enzyme and product are separate

This can be summed up as:

    1               2              3

E + S <—> ES <—> E + P

where E is the enzyme, S is the substrate, and P is the product.

In competitive inhibition, the inhibitor competes with the substrate to bind with the enzyme in state 1, making it harder to get to state 2. 

In uncompetitive inhibition, the inhibitor competes with the enzyme-substrate complex in state 2, making it harder to get to state 3. 

Mixed inhibition is like a combination of competitive and uncompetitive: the inhibitor acts on both states 1 and 2. Noncompetitive inhibition is a special case of mixed inhibition.

Vmax is the maximum rate of catalysis. When determining Vmax, we can assume that the concentration of substrate is high, and thus state 2 is the important state to consider. In uncompetitive, noncompetitive, and mixed inhibition, the inhibitor acts on state 2, decreasing [ES] even when [S] is high. Thus, Vmax decreases for these types of inhibition. In competitive inhibition, the inhibitor only acts on state 1, not state 2. With enough substrate, the same [ES] can be achieved (this is an aspect of competitive inhibition), and thus Vmax stays the same.

KM is thought of as a measure of the amount of substrate needed to get an enzyme to act at its maximum capacity. Thus, to reason about KM, we need to consider how the inhibitor is influencing the equilibrium between states 1 and 2. On the one hand, if the inhibitor causes the equilibrium to shift to the left (favoring state 1), then more substrate is needed to shift the equilibrium back to the right such that there is the same [ES] as without an inhibitor. Since more substrate is required for the same [ES] (a marker of maximum capacity), then KM increases. This is the case with competitive inhibition, since the inhibitor is competing with the substrate in state 1.

On the other hand, if the inhibitor causes the equilibrium to shift to the right (favoring state 2), when we remove substrate, the equilibrium will shift to the left such that there is the same [ES] as without an inhibitor. Thus, in this case, KM decreases. This is the case with uncompetitive inhibition, since the enzyme competes with the enzyme-substrate complex in state 2. In mixed inhibition, the inhibitor is competing with states 1 and 2, so in some cases the equilibrium will shift to the left, while in other cases, it will shift to the right. Thus, KM can increase or decrease. Noncompetitive is a special case of mixed inhibition such that KM stays the same (for this one, you may need to simply memorize the fact).

I hope this helped you gain a more intuitive understanding of enzyme inhibition kinetics so that test day is just a little bit less stressful!

Note: thanks to Berg et al.’s Biochemistry, Eighth Edition textbook, as well as Dr. Meyer’s slides in Dixie State University’s Chemistry 3510 course for giving me the tools to gain an intuitive understanding of this material.

 

The road to medical school is long, and the MCAT is one of its most formidable challenges. You will be relieved to know that what you learned in your premedical courses is actually on the test. But studying for the MCAT is more about taking that knowledge stored way back there in the nooks and crannies of your mind, bringing it to the fore, and then learning to twist and stretch it in the ways the MCAT tests. In reality, studying for the MCAT is no more (or less) difficult than spending late hours on a physics problem set or an entire weekend on an organic chemistry lab report. Just like these other tasks, the MCAT requires endurance and follow-through, but it becomes significantly more manageable when you work with a Cambridge Coaching MCAT tutor to apply a structured, systematic, and strategic approach to your studying.

Anyone can study hard - but the real key to MCAT success is learning to study smart. So, while all forms of MCAT preparation require you to crunch a lot of material, we focus on helping you to make strategic choices about your areas of focus at every step of the game. Each Cambridge Coaching tutor is a highly-skilled manager of your personal study process. He or she will do more than just target your weaknesses - your tutor’s goal is to identify the sections where you have the greatest potential for improvement, and teach you to wring every last point from them by creating the roadmap for your studying, and helping you stick to it. Right from the start, your tutor will create a customized syllabus for you, and will then modify that syllabus as needed.

Learn more about MCAT tutoringTaking the MCAT in 2021-22? Check out some other helpful blog posts below!

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Tags: MD/PhD admissions, MCAT