To quote my (somewhat pessimistic) relatives, “Nothing in life is free.” Now, young Hunter would’ve retorted, “Oh yeah? Well what about breathing? Or blinking! Or (insert any number of seemingly “free” things).” It wasn’t until I started studying the Krebs Cycle for the MCAT that I realized the truth.

Nothing in life is free. We just exchange currency from time to time. Specifically, those witty little responses I had a few decades ago DO have a cost associated with them: Energy!

Stop me if you’ve heard this one before: “The mitochondria is the powerhouse of the cell.” Well, there’s a reason it’s oversaid and cliché—because it’s true!

MCAT Prep: Navigating the Krebs Cycle

The Krebs Cycle, also known as the Citric Acid Cycle, plays a central role in catabolizing organic fuel molecules into usable energy in the form of adenosine triphosphate (ATP). Without this cycle, the energy stored in food would remain inaccessible to cells. Thus, rendering life as we know it unfeasible. 

Dramatic? Maybe, but I digress.

This cycle spins its magic within the mitochondrial matrix, oxidizing acetyl-coenzyme A (acetyl-CoA) derived from carbohydrates, fats, and proteins into carbon dioxide. More importantly, it harvests the energy released during this process to synthesize ATP.

Moreover, the Krebs Cycle acts as a nexus, linking various biosynthetic pathways. Intermediates of the cycle are siphoned off as precursors for the synthesis of amino acids, nucleotides, and other essential biomolecules, illustrating the cycle’s versatility beyond mere energy production.

For those prepping for the MCAT, the Krebs Cycle stands as a cornerstone in the realm of cellular metabolism. This cycle is not merely a sequence of reactions. Rather, it’s a beautifully orchestrated series of events that play a critical role in the cell’s energy production processes. It takes place within the mitochondria, where the true magic of biochemistry unfolds.

At its core, the Krebs Cycle is an aerobic process, meaning it requires oxygen to function properly. 

Its primary role is to oxidize acetyl-CoA, derived from carbohydrates, fats, and proteins, into carbon dioxide. In doing so, it generates high-energy molecule equivalents, which are crucial for the production of ATP (adenosine triphosphate), the cell’s main energy currency.

Further Reading

📸 A Picture Is Worth a Thousand Intermediates: How to Optimize Studying Biochemistry

🧬 What Do You Actually Need to Know for Biochemical Pathways on the MCAT?

📝 Download our free Equation Sheets with all the formulas and equations you need for Biochemistry, Physics, Organic Chemistry and Chemistry questions on the MCAT.

The Krebs Cycle Process Defined

The journey begins with the conversion of pyruvate, a product of glycolysis, into acetyl-CoA. This step, though technically not part of the Krebs Cycle, is essential for its initiation. Acetyl-CoA merges with oxaloacetate, a four-carbon molecule, to form citrate, a six-carbon compound, marking the commencement of the cycle.

MCAT Breakdown: Krebs Cycle Sequence of Events

1. Formation of Citrate: The enzyme citrate synthase catalyzes the first step, combining acetyl-CoA and oxaloacetate to form citrate.
2. Isomerization to Isocitrate: Through the action of aconitase, citrate is rearranged into isocitrate.
3. Oxidative Decarboxylation to α-Ketoglutarate: Isocitrate dehydrogenase catalyzes the oxidation of isocitrate, releasing CO₂ and producing NADH, and yielding α-ketoglutarate.
4. Oxidative Decarboxylation to Succinyl-CoA: Another CO₂ molecule is released, and NADH is produced as α-ketoglutarate is converted to succinyl-CoA by α-ketoglutarate dehydrogenase.
5. Conversion to Succinate: Succinyl-CoA synthetase converts succinyl-CoA into succinate, generating ATP or GTP in the process.
6. Oxidation to Fumarate: Succinate is then oxidized to fumarate by succinate dehydrogenase, producing FADH₂.
7. Hydration to Malate: Fumarase adds water to fumarate, forming malate.
8. Oxidation to Oxaloacetate: Finally, malate is oxidized to oxaloacetate by malate dehydrogenase, producing NADH and completing the cycle.
   

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Input and Output Products

Input Products:

• Acetyl-CoA
• Water
• NAD⁺
• FAD

Output Products:

• 2 molecules of CO₂
• 3 molecules of NADH
• 1 molecule of FADH₂
• 1 molecule of ATP or GTP
• Regenerated oxaloacetate

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Enzymatic Reactions

Each step within the Krebs Cycle is catalyzed by a specific enzyme, ensuring the cycle proceeds efficiently and effectively. These enzymes facilitate the transformation of substrates into products. Additionally, they play a regulatory role, ensuring the cycle adjusts to the metabolic needs of the cell.

Understanding all the MCAT Krebs Cycle concepts is paramount for premed students, as it lays the foundation for comprehending more complex physiological and pathological processes encountered in medical studies and medical school. 

However, don’t stress too much! You’ll notice that most of the enzyme names are pretty much the reactant + the reaction type. 

For example, the enzyme that converts fumarate is called fumarase, isocitrate is affected by isocitrate dehydrogenase, etc etc. By keeping this in mind you can remember most, if not all, of the enzymatic reactions in the Krebs Cycle, but only have to memorize half of the content!

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Final Thoughts

At the end of the day, the Krebs Cycle stands not just as a biochemical pathway but as a beacon of life’s resilience and adaptability. It is a fundamental process that fuels the cellular machinery and intertwines with life’s myriad forms.

Through its elegant complexity, the Krebs Cycle reminds us of the intricate interdependence of all living organisms and the fragile equilibrium that sustains life on Earth.

However, if that’s not enough of a reason to appreciate the Krebs Cycle, then consider this; it’s more than likely going to show up on your MCAT!

Need some help with biochem concepts? We break down the Krebs Cycle for the MCAT in our Blueprint MCAT modules and live classes!

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