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Third-Year Medical Student, Lewis Katz School of Medicine at Temple University
Reviewed: 4/25/24
Are you studying for the citric acid cycle for the MCAT and unsure about where to begin? Are you also wondering what the Krebs cycle is? Read on to learn more!
The citric acid cycle, also known as the Krebs or tricarboxylic acid cycle, probably goes by so many names because of its importance. It is the primary process where the food we eat is converted into energy our body can use to grow, digest, move, and carry out any other essential function.
If you’ve started studying carbohydrate metabolism for the MCAT, you probably already know how essential the Krebs cycle is in understanding the human body. This article will explain what you should learn about the Krebs cycle as an aspiring medical professional, from the basics to the specific steps involved.
The Krebs cycle is part of a broader process called cellular respiration, which refers to the chemical reactions that harvest energy from the foods we eat into energy that our cells can use. Cellular respiration contains three main subparts: glycolysis, the total reaction for the citric acid cycle, and oxidative phosphorylation.
The Krebs acid cycle is the main energy producer in cellular respiration. It does so through acetyl-CoA oxidation derived from glycolysis into NADH, FADH2, and CO2. How do these products translate into energy? Read below to learn about the citric acid cycle on the MCAT.
NAD+ and FADH are small molecules referred to as electron shuttles. They have the amazing ability of carrying and donating their high-energy electrons to the electron transport chain.
NAD+ and FADH are reversibly reduced into NADH and FADH2 throughout cellular respiration, meaning they gain electrons.
The electron transport chain is part of oxidative phosphorylation, the final destination of cellular respiration. It uses the electrons from NADH and FADH2 from the Krebs cycle to produce 32 molecules of ATP.
Once NADH and FADH2 are oxidized (or, in other words, lose their electrons) to the electron transport chain, they revert into NAD+ and FAD+ electron shuttle molecules. They can then be reused in other parts of cellular respiration.
Adenosine triphosphate, or ATP, is a high energy-carrying molecule that fuels the cellular processes vital to all living things. ATP is broken down to release and transfer the energy a cell requires, and its phosphoryl group is removed in hydrolysis.
ATP is one of the main final products of the cellular respiration cycle. Looking at the big picture, ATP captures the chemical energy from the breakdown of glucose and converts it into cellular fuel. NADH and FADH2 are intermediate molecules in this process.
Below are the eight stages of the citric acid cycle substrates, explaining what occurs before and after it to add necessary context. For expert advice on the citric acid cycle, book a free consultation with Inspira Advantage.
Source: Khan Academy
The Krebs cycle is part of the more extensive process of cellular respiration. Glycolysis is the first step of cellular respiration and is where a 6-carbon glucose molecule is broken down into two 3-carbon pyruvate molecules in the cytosol. ATP and NADH are also released in the process.
Pyruvate enters the mitochondrial matrix and is broken down and combined with an enzyme called coenzyme A, or CoA for short. This reaction results in acetyl-CoA, releasing CO2 as a waste product we exhale.
Through a series of steps, this cycle sequesters the energy in the bonds of acetyl-CoA and transfers it into NAD+ and FADH, reducing them into NADH and FADH2. These molecules eventually go through oxidative phosphorylation, transforming the trapped energy within them into high-energy molecules of ATP.
Described below is each step of the cycle.
Step 1: The cycle starts when an enzyme facilitates the merging of acetyl-CoA with the four-carbon molecule oxaloacetate. This results in the 6-carbon molecule citric acid.
As described in the subsequent steps, the carbon atoms in citric acid continue circulating through the cycle in reactions that release energy the electron shuttles capture.
Step 2: Citric acid loses and then gains a water molecule, converting it into its isomer isocitrate, another 6-carbon molecule.
Step 3: Isocitrate is oxidized, resulting in the removal of a carbon atom. This reaction leads to the generation of a five-carbon-molecule, α-ketoglutarate, and a CO2 molecule (that was formed by combining the lost carbon atom with oxygen). This oxidation process produces two available electrons that reduce NAD+ into a high-energy NADH molecule.
Step 4: The above step is repeated in which α-ketoglutarate is oxidized and decarboxylated, resulting in the four carbon molecules succinyl-CoA, a CO2, and an NADH molecule.
Step 5: Succinyl-CoA is rearranged into a more energy-conserving molecule, succinate. The energy released is used to phosphorylate GDP to GTP, a high-energy molecule equivalent to ATP.
Step 6: Succinate is converted to fumarate, another four-carbon molecule, in a dehydration reaction. The hydrogen atoms released combine with FAD to produce FADH2, which goes on to donate its electrons to the electron transport chain directly.
Step 7: Water is added to fumarate, producing the four-carbon molecule L-malate.
Step 8: A hydrogen molecule is removed from L-malate in an oxidation reaction, which results in the regeneration of oxaloacetate. The energy released leads to the production of an NADH molecule.
Oxaloacetate is now available for the next turn of the cycle. This is why it's called a cycle- it begins and ends with the same molecule. Recall that glycolysis produces two pyruvate molecules, but only one pyruvate molecule goes through the cycle at a time.
The equation of the cycle summarizes the output of the steps above:
1 Acetyl-CoA + 3 NAD+ + 1 FAD + 2 H2O + 1 GDP + 1 P → 1 CoA-SH + 3 NADH + 1 FADH2 + 2 CO2 + 1 GTP + 3 H+
After this cycle, NADH and FADH2 go through oxidative phosphorylation to the electron transport chain. Here, these molecules donate their high-energy electrons to spearhead the synthesis of ATP from ADP- 32 total ATPs per glucose molecule that enters glycolysis.
For every NADH and FADH2 molecule produced, 2.5 and 1.5 ATPs are produced in the electron transfer chain, respectively.
Still have questions about the Krebs cycle on the MCAT? Take a look at our answers to some frequently asked questions.
When memorizing this cycle, focus on the big picture first and narrow in on the details later. For example, consider what the cycle is for to release stored energy that the cell can use.
Then begin memorizing the steps where NADH and FADH are produced.
Quizzes and the memory palace technique are also effective ways to memorize the Krebs cycle for the MCAT.
The Kreb cycle will be on the Biological and Biochemical Foundations of Living Systems section of the MCAT, which consists of 59 total questions.
You will be tested on this cycle on the MCAT. You will likely not need to know tiny details such as the enzymes used and the specific structures of the intermediate molecules, but you should know details such as the carbon count throughout the cycle.
The Krebs cycle is a vital metabolic pathway for cellular respiration. Here are the key points you need to know about the Krebs cycle on the MCAT:
The above are just the main points. You will need to cover this extensively while studying for the MCAT.
The Krebs cycle takes place in the mitochondria of eukaryotic cells. The mitochondria are often called the "powerhouses" of the cell due to their role in generating ATP, and the Krebs cycle is a key part of this energy production process.
There are many products of this cycle that are produced during a series of reactions.
These products, including ATP, NADH, FADH2, carbon dioxide, and oxaloacetate, are important for cellular energy production and further participation in oxidative phosphorylation to generate ATP through the electron transport chain.
When you first start learning about the citric acid cycle for the MCAT, there is a lot to take in. But the great thing about this metabolic pathway is that there is a lot of logic and common sense to its inputs and outputs-–it is a cycle, after all!
Once you start understanding the overall purpose of the Krebs cycle, you’re on your way to acing carbohydrate metabolism!
The next step is to use Inspira Advantage's free practice tests to apply and assess your knowledge!
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