TCA Cycle (Tricarboxylic Acid Cycle): Biochemistry, Metabolism, Enzymes

What Is The TCA Cycle?

The TCA cycle is also called the Krebs or citric acid cycle. It is one of the most basic metabolic pathways of cellular respiration. The process is the second step in aerobic respiration in the mitochondrial matrix of eukaryotic cells. The TCA cycle is the pathway through which the complete oxidation of acetyl-CoA, originating from carbohydrates, fats, and proteins, takes place into carbon dioxide and energy.

Overview Of The TCA Cycle

The TCA cycle is an aerobic pathway that produces high-energy electron carriers, NADH and FADH2, crucial for the production of ATP in the electron transport chain. The cycle functions as a closed loop, regenerating at the end of its starting molecule, oxaloacetate. As such, it is constantly regenerated so that the cycle may continue so long as supplies of acetyl-CoA are available.

Steps Of The TCA Cycle

Now, there are a total of eight major steps involved in the cycle of the TCA cycle, each of which is catalyzed by specific enzymes. These include citrate formation—one in which acetyl-CoA is combined with the four-carbon compound oxaloacetate to form the six-carbon compound citrate while releasing the CoA group—and isomerization, where citrate is converted into isocitrate in a two-step process involving the loss, followed by the gain, of a water molecule.

1. Oxidative Decarboxylation: Isocitrate gets oxidized into alpha-ketoglutarate by releasing one carbon dioxide molecule and reducing NAD+ into NADH. The catalyst of this reaction is isocitrate dehydrogenase.

2. Further Decarboxylation: Alpha-ketoglutarate is oxidized while reducing NAD+ into NADH, and another carbon dioxide molecule is released, together with the formation of a four-carbon compound known as succinyl-CoA, catalyzed by alpha-ketoglutarate dehydrogenase.

3. Substrate-Level Phosphorylation: Succinyl-CoA is converted to succinate, and a phosphate group is transferred to ADP to produce ATP (or GTP).

4. Oxidation of Succinate: In this step, succinate gets oxidized to form fumarate, with two hydrogen atoms transferred to FAD to result in FADH2.

5. Hydration: A water molecule is added to fumarate, converting it to malate.

6. Final Oxidation: Malate gets oxidized to again result in oxaloacetate, producing another NADH in the process.

End Products Of The TCA Cycle

The products of each cycle of the TCA are:

1. 6 NADH: Those are the high-energy electron carriers that will feed into the electron transport chain.

2. 2 FADH₂: Another electron carrier

3. 2 ATP; IP: Those are products of substrate-level phosphorylation.

4. 4 CO₂: It is carbon dioxide, a waste product in the cycle.

Importance Of The TCA Cycle

There are several reasons that the TCA cycle is important :

1. Energy production: It generates NADH and FADH₂ for ATP synthesis on the electron transport chain.

2. Biosynthesis: The TCA cycle intermediates act as precursors in the synthesis of amino acids, nucleotides, and other biomolecules.

3. Production of Carbon Dioxide: Carbon dioxide is generated in this cycle and is exhaled out from the body through respiration.

TCA Cycle Regulation

The TCA cycle is strictly regulated so the rate of energy production within the cell can be adjusted to the metabolic needs of the cell. Regulation of the TCA cycle exists at several key enzymes, including :

1. Citrate Synthase: Controls entry of acetyl-CoA into the cycle.

2. Isocitrate Dehydrogenase: It is inhibited by the levels of NADH and ATP. Thus, it makes isocitrate's conversion to alpha-ketoglutarate controlled.

3. Alpha-Ketoglutarate Dehydrogenase: The same type of control occurs for this enzyme as for isocitrate dehydrogenase. This is to maintain energy production in balance with the availability of substrates.

The Connection Between Glycolysis And The TCA Cycle

The TCA cycle is also directly linked with glycolysis because the products of the latter get converted into acetyl-CoA. As soon as the glycolysis has taken place in the cytoplasm, pyruvate is transported into the mitochondria, where it undergoes oxidation decarboxylation to produce acetyl-CoA. This acetyl-CoA then enters the TCA cycle for further oxidation and thus energy production.

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