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The TCA cycle (tricarboxylic acid cycle) or the Krebs cycle, also known as the citric acid cycle (CAC) is a series of chemical reactions used by all organisms that respire (as opposed to organisms that ferment) to release stored energy through the oxidation of acetyl CoA derived from carbohydrates, fats, and proteins into ATP. It was proposed by German-born British Biochemist Sir Hans Adolf Krebs.
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Keyterms: TCA Cycle, Tricarboxylic acid cycle, Krebs cycle, Citric acid cycle, Oxidation, Acetyl CoA, carbohydrates, fats, proteins, ATP, respiration, NADH, FADH2, electrons
TCA Cycle Overview
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TCA Cycle is a process through which energy is generated by the respiration of organisms. Energy is generated either by anaerobic respiration or aerobic respiration. The cycle is of central importance to many biochemical pathways and it provides precursors of certain amino acids, as well as the reducing agent NADH and FADH2 that are used in numerous other reactions. Each of these compounds transfers its electrons to the next pathway bringing about oxidation.

TCA Cycle
The electrons help in bringing about the transfer oxidation in the reaction. It takes place in the matrix of mitochondria in the second phase of cellular respiration. All the enzymes that catalyze the reactions in the TCA cycle are soluble. This cycle directly produces less amount of ATP or energy molecules. It is also a cyclic pathway because the last step regenerates the first molecules of the pathway thus making it a closed loop and the whole process happens in the presence of oxygen.
Also Read: Energy Currency of the Cell
Steps of TCA Cycle
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It is an eight-step pathway and plays a major role in the breakdown of organic molecules. Macromolecules such as sugar, fatty acid, glucose, amino acids, etc. which cannot directly enter the TCA cycle, are first broken down into a two-carbon compound called Acetyl CoA. This can enter the TCA cycles and it undergoes other chemical reactions to produce carbon dioxide and energy. A soluble enzyme helps in catalyzing every step of the pathway.
Oxidation of Pyruvate – Pyruvate which is derived from glucose undergoes oxidation to give acetyl CoA and this enters the cycle to give rise to a series of reactions. These are as follows-
Step 1 – Acetyl CoA which is a two-carbon molecule compound, combined with a four-carbon compound called oxaloacetate. This reaction releases the CoA group resulting in the formation of a six-carbon molecule called citrate.
Step 2 – In the next step, citrate gets converted into an isomer of citrate called the isocitrate. This is a two-step process and occurs simultaneously. A citrate molecule first loses a water molecule and then gains one to form isocitrate.
Step 3 – In this step isocitrate oxidises and a molecule of carbon dioxide is released thus leaving behind a five-carbon molecule, ?-ketoglutarate. NAD+ also gets reduced to NADH. This entire reaction is catalyzed by the enzyme, isocitrate dehydrogenase.
Step 4 – In this step oxidation of ?-ketoglutarate occurs, releasing a molecule of carbon dioxide and reducing NAD+ to NADH. The remaining four-carbon molecules take up the CoA and form Succinyl CoA which is considered as an unstable compound. This entire reaction is catalyzed by the enzyme called ?-ketoglutarate.
Step 5 – The CoA from Succinyl CoA is replaced with a phosphate group. It then gets transferred to ADP to produce the required ATP molecules. A four-carbon molecule called Succinate is also produced in this step.
Step 6 – In this step oxidation of Succinate occurs to give rise to fumarate. Two hydrogen atoms are transferred to FAD giving rise to FADH2. This product then transfers its electrons directly to the electron transport chain (ETC) as the enzyme carrying out (catalyzing) the reaction is embedded in the inner membrane of mitochondria.
Step 7 – This step involves the addition of a water molecule to fumarate that converts to produce malate with the help of an enzyme called Fumarase.
Step 8 – In this last step, the oxidation of malate occurs that gives rise to oxaloacetate which is a four-carbon compound, and another molecule of NAD+ is also reduced to NADH. This entire reaction is catalyzed by the enzyme, Malate Dehydrogenase.
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End Products of TCA Cycle
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One cycle of this citric acid cycle generates the following end products –
- Two molecules of carbon dioxide.
- One molecule of GTP.
- Three molecules of NADH, three hydrogen ions, one molecule of FADH.
- One molecule of ATP.
Also Read: Difference between Photosynthesis and Respiration
Things to Remember
- From acetyl CoA, two molecules of carbon enter the pathway, and subsequently, two molecules of carbon dioxide are released.
- It should also be noted that since one glucose molecule gives rise to two molecules of Acetyl CoA thus the total end products get doubled i.e. in total six molecules of NADH, three hydrogen ions, two molecules of FADH?, and two molecules of ATP are produced.
- The TCA cycle forms the main source of energy for cells and plays an important role in aerobic respiration.
- Macromolecules such as sugar, fatty acid, glucose, amino acids, etc. which cannot directly enter the TCA cycle, are first broken down into a two-carbon compound called Acetyl CoA which are further synthesized through other chemical reactions and forms energy and carbon dioxide.
Sample Questions
Ques. Why is the TCA Cycle an Amphibolic Pathway? (2 marks)
Ans. A pathway that serves both as a catabolic, as well as an anabolic pathway, is known as an Amphibolic Pathway. In the TCA cycle, the reaction between Coenzyme A and citrate follows an anabolic pathway and further steps follow the catabolic pathway. Hence this cycle is called an Amphibolic pathway.
Ques. What is the importance of the TCA Cycle? (2 marks)
Ans. Although only 2 AT molecules are produced per cycle of this process, it contributes to the release of many ATP molecules indirectly with the help of NADH and FADH2 generated in the cycle. These products both are electron carriers and they deposit their electrons into the next step through the redox reaction. Through oxidative phosphorylation, the synthesis of ATP molecules happens. This 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.
Ques. Who first proposed this cycle? (1 mark)
Ans. The German-born British Biochemist Sir Hans Adolf Krebs first proposed this cycle in 1937, which he named a citric acid cycle. He received the 1953 Nobel Prize in Physiology or Medicine for his work.
Ques. Who furthered the understanding of the process of this cycle? (1 mark)
Ans. Though Krebs elucidated most of the reactions in this pathway, the discovery of coenzyme A in 1945 by Fritz Lipmann and Nathan Kaplan allowed researchers to work out the cycle of reactions as it is known today.
Ques. In which step is the ATP molecule produced? (1 mark)
Ans. In step 5, one molecule of the adenosine triphosphate (ATP) that powers most cellular functions, is produced.
Ques. Name the three regulatory enzymes in the TCA cycle. (3 marks)
Ans. The three regulatory enzymes in the TCA cycle are:
- Citrate synthase
- Isocitrate dehydrogenase
- Alpha ketoglutarate dehydrogenase
Ques. State the number of ATP produced during a TCA cycle and when? (2 marks)
Ans. The number of ATP produced during a TCA cycle per glucose molecule is 2.
The production of ATP takes place when the Succinyl CoA generates succinate through the synthetase of the enzyme succinyl CoA.
Ques. Where does the TCA cycle take place? (1 mark)
Ans. The TCA cycle takes place in the mitochondrial matrix in the eukaryotes and in the cytosol in the prokaryotes.
Ques. What is the function of the TCA cycle? (1 mark)
Ans. TCA cycle is a part of metabolism that is utilized by the aerobic organisms in order to produce cellular energy and biosynthetic intermediates.
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