Citric Acid Cycle

Описание: Need help preparing for the Bio/Bio Chemistry section of the MCAT? MedSchoolCoach expert, Ken Tao, will teach everything you need to know about the Citric Acid Cycle of Cellular Respiration for the biochemistry section of the MCAT. Watch this video to get all the MCAT study tips you need to do well on this section of the exam!

The citric acid cycle, also known as the TCA cycle or the Krebs cycle, is a series of chemical processes used by aerobic organisms in order to break down carbon fuels into carbon dioxide, water, and energy.

The first step of the cycle is the formation of citrate. In this Step, acetyl-CoA donates its acetyl group, consisting of two carbons, to oxaloacetate, which is a 4-carbon molecule. This process forms citrate, which is a 6-carbon molecule. Furthermore, this reaction is catalyzed by the enzyme citrate synthase. Also note that anytime a molecule is bound to coenzyme A, it is bound by a thioester bond. Hydrolysis of a thioester bond is highly exergonic and releases a high amount of free energy. This reaction is essential for driving a lot of endergonic or unfavorable processes. In this instance, it is helpful because usually, the oxaloacetate concentration in the mitochondrial matrix is relatively low, and the highly exergonic hydrolysis of the thioester bond helps to push this reaction forward.

The second step of the citric acid cycle is the formation of isocitrate. In this reaction citrate is isomerized to isocitrate, and it is catalyzed by the enzyme aconitase. Also, an intermediate called cis-aconitate is produced as well. Therefore, this step involves two separate reactions. The first reaction, citrate to cis-aconitate, is a dehydration reaction as water is being released. The subsequent reaction, cis-aconitate to isocitrate, is a hydration reaction, in which water is added to form a new molecule.

The third step in the cycle is the oxidative decarboxylation of isocitrate. Recall that oxidative decarboxylation means that a compound will be oxidized and decarboxylated to form a new compound. In this case, isocitrate is oxidized, and then it is decarboxylated to form α-ketoglutarate and carbon dioxide. Note that one of the carbons from the acetyl group of isocitrate and acetyl-CoA is released as carbon dioxide. Also, as isocitrate is being oxidized, NAD+ is reduced to NADH. The NADH will be used for producing ATP in the electron transport chain. This reaction is catalyzed by the enzyme isocitrate dehydrogenase.

The fourth step involves another oxidation-decarboxylation reaction. This time, α-ketoglutarate is oxidized and decarboxylated to form succinyl-CoA and carbon dioxide. Also, NAD+ is reduced to NADH. The reaction is catalyzed by the enzyme α-ketoglutarate dehydrogenase complex. Interestingly, the activity of α-ketoglutarate dehydrogenase complex, also known as oxoglutarate dehydrogenase, is reduced in the brain of patients with Alzheimer’s disease. This reduction leads to the possibility that the TCA cycle is unable to function in these individuals, which may lead to the build-up of toxic chemicals in the brain.

At this point in the cycle, two carbons have been removed from an acetyl group and acetyl-CoA. Both carbons have been used to produce carbon dioxide, so essentially completing the oxidation of glucose. In the fifth step of the TCA cycle, the molecule succinate is hydrolyzed from a thioester bond and succinyl-CoA. This reaction is also highly exergonic.

In the sixth step of the citric acid cycle, succinate is oxidized to fumarate. At the same time, FAD is reduced to FADH2. This reaction is catalyzed by the enzyme succinate dehydrogenase. One important thing to note is that succinate dehydrogenase is the only enzyme of the citric acid cycle that participates in both the citric acid cycle and the electron transport chain.

The seventh step of the cycle is the hydration of fumarate. As previously mentioned, hydration means the addition of water. In this case, water is added to fumarate to form malate. This reaction is catalyzed by the enzyme fumarase. One interesting note is that fumarase is present in many tissues throughout the body, and mutations in this enzyme have been linked to several diseases such as smooth muscle tumors, and even renal cell cancer.

In the last step of the citric acid cycle, the molecule malate is oxidized to oxaloacetate. Also, NAD+ is reduced to NADH. The citric acid cycle starts with the generation of oxaloacetate and ends with its regeneration. As long as acetyl-CoA is present in the body, the citric acid cycle will run continuously.

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