Are you studying for the citric acid cycle for the MCAT and unsure about where to begin? Read on to learn what you should know about this metabolism pathway.
The citric acid cycle, also known as the Krebs cycle or the tricarboxylic acid cycle, probably goes by so many names because of just how important it is. 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 you can think of.
If you’ve started studying carbohydrate metabolism for the MCAT, you probably already know how essential the citric acid cycle is in understanding the human body. In this article, we’ll break down what you should learn about the citric acid cycle as an aspiring medical professional, from the basics to the specific steps involved.
The citric acid cycle is a part of a broader process called cellular respiration, which refers to the chemical reactions that harvest energy from the foods that we eat into energy that our cells can use. Cellular respiration contains three main subparts: glycolysis, the citric acid cycle, and oxidative phosphorylation.
The citric acid cycle is the main energy producer in cellular respiration. It does so through the oxidation of acetyl-CoA derived from glycolysis into NADH, FADH,and CO. How do these products translate into energy? Read below to find out how.
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 FADHthroughout cellular respiration, meaning that 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 FADHfrom the citric acid cycle to produce 32 molecules of ATP.
Once NADH and FADH 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. To release and transfer the energy required by a cell, ATP is broken down, and its phosphoryl group is removed in a process called hydrolysis.
ATP is one of the main final products of the cellular respiration cycle. Looking at the big picture, then, ATP captures the chemical energy from the breakdown of glucose and converts it into cellular fuel, and NADH and FADH2are intermediate molecules in this process.
Below, the eight steps of the citric acid cycle are outlined, with explanations of what occurs before and after it to add necessary context.
The citric acid 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 then further broken down and combined with an enzyme called coenzyme A, or CoA for short. This reaction results in acetyl-CoA, releasing CO as a waste product that we exhale out.
Through a series of steps, the citric acid cycle sequesters the energy in the bonds of acetyl-CoA and transfers it into NAD+ and FADH, reducing them into NADH and FADH. These molecules eventually go through oxidative phosphorylation, in which the trapped energy within them is transformed into high-energy molecules of ATP.
Described below is each step of the citric acid 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- understand why it's called the citric acid cycle now?
As described in the subsequent steps, the carbon atoms in citric acid continue to circulate through the cycle in reactions that release energy captured by the electron shuttles. The key to understanding the citric acid cycle is following how these carbons are rearranged because it is in this rearrangement that energy is released, which is the purpose of cellular respiration.
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 CO molecule (that was formed by combining the lost carbon atom with oxygen). This oxidation process results in 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, as well as a CO 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 FADH, which goes on to directly donate its electrons to the electron transport chain.
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 citric acid 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 molecules go through the citric acid cycle at a time.
The equation of the citric acid cycle summarizes the output of the steps above:
1 Acetyl-CoA + 3 NAD+ + 1 FAD + 2 HO + 1 GDP + 1 P → 1 CoA-SH + 3 NADH + 1 FADH+ 2 CO+ 1 GTP + 3 H+
After the citric acid cycle, NADH and FADH make their way through oxidative phosphorylation to the electron transport chain. It is here where these molecules donate their high energy electrons to spearhead the synthesis of ATP from ADP- 32 total ATPs in fact, per glucose molecule that enters glycolysis. For every NADH and FADH molecule produced, 2.5 and 1.5 ATPs are produced in the electron transfer chain, respectively.
Still have questions about the citric cycle on the MCAT? Take a look at our answers to some frequently asked questions.
When memorizing the citric acid cycle, focus on the big picture first and narrow in on the details later. For example, first consider what the citric acid cycle is for- to release stored energy that the cell can use. Then ask how it does so? By transferring energy from acetyl-CoA to energy shuttles NADH and FADH. Then begin memorizing the steps where NADH and FADH are produced.
The citric acid cycle will be on the Biological and Biochemical Foundations of Living Systems section of the MCAT, which consists of 59 total questions.
Yes, you will be tested on the citric acid cycle on the MCAT. You most likely will 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.
There is a lot to take in when you first start learning about the citric acid cycle for the MCAT. 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 citric acid cycle, you’re on your way to acing carbohydrate metabolism!