The series of chemical reactions taking place in cells of all aerobic organisms to release energy which is stored in the form of ATP by conversion of Acetyl CoA derived from carbohydrates, fats, and proteins are defined as the TCA cycle or Tricarboxylic Acid Cycle. It is also known as the Citric Acid cycle and it takes place in mitochondria in the second phase of cellular respiration. Soluble enzymes catalyze the reactions in the TCA cycle.
It is a common anaerobic pathway giving NADH and FADH2. Each of these transfers their electrons to the next pathway bringing about the oxidation. Without the electron, transfer oxidation will not take place. TCA Cycle directly produces less amount of ATP or energy molecules. And it is a cyclic pathway because the last step regenerates the first molecules of the pathway thus making it a closed loop. It occurs in the presence of oxygen.
The TCA Cycle or Citric Acid cycle was proposed by British Biochemist Sir Hans Adolf Krebs. Krebs elucidated most of the reactions in this pathway and also received recognition for his work. Furthermore, Fritz Lipmann and Nathan Kaplan discovered Coenzyme A later letting other researchers work out the complete cycle as we know it today.
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The TCA cycle is an eight-step pathway that plays a major role in the breakdown of organic molecules. Macromolecules like glucose, sugars, fatty acids, amino acids, etc. cannot directly enter the TCA cycle. Thus, they are first broken down into two-carbon compound Acetyl CoA. After Acetyl CoA enters the TCA cycles, it undergoes other chemical reactions to produce carbon dioxide and energy. Every step of the pathway is catalyzed by a soluble enzyme.
Pyruvate derived from glucose undergoes oxidation to give acetyl CoA. Acetyl CoA thus enters the cycle and a series of reactions follows
Acetyl-CoA which is a two carbon molecules compound, combines with a four-carbon compound, oxaloacetate, resulting in the formation of a six-carbon molecule called citrate and releases the CoA group.
In the next step, citrate gets converted into an isomer of citrate called- isocitrate. Two processes simultaneously occur in this step. At first, citrate loses a water molecule and again gains it to form isocitrate.
The third step oxidation of isocitrate occurs. A five-carbon molecule called ɑ-ketoglutarate is left behind with the release of a molecule of carbon dioxide is released. NAD+ also gets reduced to NADH. This step is catalyzed by the enzyme isocitrate dehydrogenase.
In this step, ɑ-ketoglutarate is oxidized, releasing a molecule of carbon dioxide and reducing NAD+ to NADH. Simultaneously, CoA is picked up by the remaining four-carbon molecules forming Succinyl CoA which is an unstable compound. This step is catalyzed by the enzyme ɑ-ketoglutarate.
The phosphate group replaces CoA from succinyl CoA. It then gets transferred to ADP to give rise to the ATP molecule. This step also gives a four-carbon molecule- Succinate.
In this step, Succinate is oxidized to give fumarate. Also, two hydrogen atoms are transferred to FAD giving rise to FADH2. FADH2 then transfers its electrons directly to the electron transport chain (ETC) as the enzyme that catalyzes this reaction is embedded in the inner membrane of mitochondria.
A water molecule is added to fumarate and fumarate gets converted to malate with the help of enzyme Fumarase.
In this step of the cycle, the oxidation of malate regenerates oxaloacetate which is a four-carbon compound, and another molecule of NAD+ is reduced to NADH. This step is catalyzed by the enzyme Malate Dehydrogenase.
One cycle of Citric Acid generates the following end products-
Two molecules of carbon dioxide
Three molecules of NADH, three hydrogen ions, one molecule of FADH₂
One molecule of GTP
Two carbon molecules enter from acetyl CoA in the pathway, and two molecules of carbon dioxide are released. Three molecules of NADH, three hydrogen ions, one molecule of FADH₂ are produced and One molecule of ATP is produced.
It should be noted that one glucose molecule gives rise to two molecules of Acetyl CoA. Thus, the total end products get doubled.
1. What is the Importance of the TCA Cycle?
Although the ATP generated directly in one TCA cycle is very less (2 molecules of ATP per cycle), it contributes to the release of many ATP molecules indirectly with the help of NADH and FADH2 generated in the cycle. Both of these are electron carriers and they deposit their electrons into the electron transport chain (ETC) to drive the synthesis of ATP molecules through oxidative phosphorylation. TCA cycle acts as a final oxidative pathway for the breakdown of carbohydrates, proteins, lipids, amino acids, via Acetyl CoA, or other intermediates of the cycle.
2. Why is the TCA Cycle an Amphibolic Pathway?
An amphibolic pathway is the one that serves as a catabolic as well as an anabolic pathway. In the TCA cycle, the Reaction of Coenzyme A with citrate is anabolic is an anabolic pathway and further steps follow the catabolic pathway. Hence TCA cycle called an Amphibolic pathway