Tricarboxylic Acid Cycle (TCA): Meaning, Outline and Significance

In this article we will discuss about:- 1. Meaning of Tricarboxylic Acid Cycle 2. Outline of TCA Cycle 3. Significance.

Meaning of Tricarboxylic Acid (TCA) Cycle:

Tricarboxylic acid cycle (TCA cycle) is also called citric acid cycle or Krebs cycle (after its discoverer, Sir Hans Krebs). TCA cycle or citric acid cycle is the central metabolic hub of the cell and is the gateway to the aerobic metabolism of any molecule that can be transformed into an acetyl group or dicarboxylic acid.

In glycolysis  the glucose molecule is broken down in pyruvate. Although the pyruvate is converted to various fermentation products as a result of fermentation, it is oxidized fully to CO₂ in respiration.

Outline of TCA Cycle:

Though the breakdown of glucose to pyruvate by earlier described pathways (glycolysis, HMP pathway, ED pathway) yields some energy, it is the degradation of pyruvate aerobically to CO₂ via TCA cycle (an eight step process) that generates much more of the energy because the TCA cycle is one major pathway by which pyruvate is completely oxidized to carbon dioxide (CO₂).

Pyruvate is first decarboxylated and converted into acetyl-CoA, which the connecting link between glycolysis and TCA cycle and acts as the fuel for TCA cycle. Acetyl-CoA is a two carbon energy-rich molecule, which initiates TCA cycle (Fig. 24.4) and is condensed with a four-carbon intermediate, oxaloacetate, to form citrate and to begin the six-carbon stage.

The citrate is isomerized to give isocitrate, which is subsequently oxidized and decarboxylated twice to produce α-ketoglutarate, then succinyl-CoA. During it, two NADH molecules are generated and two carbons are released from the cycle as CO₂ and, as a result, four-carbon stage initiates. Succinyl-CoA is finally converted into oxaloacetate via the formation of succinate, fumarate and L-malate.

Four-carbon stage yields one FADH₂ (FAD = Flavin adenine dinucleotide) and one NADH (NAD = Nicotinamide dinucleotide) during two oxidation steps: succinate to fumarate and L-malate to oxaloacetate. GTP (a high energy molecule equivalent to ATP) is also produced during the conversion of succinyl-CoA to succinate. Finally, the oxaloacetate is reformed and becomes ready to join acetyl-CoA to proceed further.

In this way, Kreb’s cycle (TCA-cycle) generates two CO₂ molecules, three NADH molecules, one FADH₂ molecule and one GTP molecule for each acetyl-CoA molecule oxidized in the cycle.

The generation of NADH and FADH₂ molecules is associated with electron transport chain and oxidative phosphorylation. The generation of GTP molecule takes place via substrate-level phosphorylation.

The various reactions of TCA cycle and enzymes involved are given in Table 24.1.

However, the overall reaction of the TCA cycle is:

Acetyl – CoA + 3 NAD + FAD + GDP + Pi + 2H₂ O → 2CO₂ + 3 NADH + FADH₂ + GTP + 2H⁺+ CoA

Significance of TCA Cycle:

TCA cycle, as stated, is a central hub in cellular metabolism. It is the gateway to the aerobic metabolism of any molecule that can be transformed into an acetyl group or dicarboxylic acid.

Although the cycle generates considerable amount of energy, its major function is to provide precursors, not only for the strong forms of fuel, but also for the building blocks of many other molecules such as amino acids, nucleotide bases, cholesterol and porphyrin.

For example, most of the carbon atoms in oorphyrins (the organic components of heme) come from succinyl-CoA. Many of the amino acids are derived from α-ketoglutarate and oxaloacetate as shown in the following. Thus the TCA cycle is an amphibolic cycle, which means that it functions not only in catabolism (breakdown) but also in anabolic (synthesis) reactions in the cell.