19.4: The Citric Acid Cycle: Overview

In aerobic organisms, the citric acid cycle is the second stage of cellular respiration wherein molecules derived from the breakdown of carbohydrates, proteins, and fats are oxidized into carbon dioxide and energy. This process is also known as the tricarboxylic acid (TCA) cycle as the first product of the cycle, citric acid, contains three carboxyl groups in its structure. Alternatively, this cycle is also referred to as the Krebs cycle, in honor of its discoverer Sir Hans Krebs.

The citric acid cycle begins when complex molecules, such as glucose, are broken down into simpler molecules, such as acetyl groups. The acetyl groups then combine with a four-carbon molecule called oxaloacetate to form a six-carbon compound, citric acid. During the cycle, citric acid is rearranged and two of its carbon atoms are removed, accompanied by the release of two molecules of carbon dioxide and four electrons. At the end of the cycle, a molecule of oxaloacetate is produced, which then combines with another acetyl group to start the next round of the cycle.

The majority of the intermediates on which the cycle is dependent are components of other biochemical pathways that produce metabolites such as porphyrins, fatty acids, and amino acids. If any of these intermediates are diverted, the cycle's integrity is compromised, and the cycle comes to a halt.

The citric acid cycle, also known as the tricarboxylic acid cycle or the Krebs cycle, is the second phase of cellular respiration that oxidizes biomolecules to produce energy.

It occurs in the mitochondrial matrix in eukaryotes and within the cytosol in prokaryotes.

Pyruvate, the end product of glycolysis, combines with coenzyme A, generating acetyl coenzyme A or acetyl-CoA.

Then, the enzyme citrate synthase initiates the cycle by condensing acetyl-CoA and oxaloacetate to form the first product, citric acid.

In the second step, aconitase rearranges citric acid to its easily oxidizable isomer, isocitrate.

The third step involves oxidation of isocitrate to α-ketoglutarate by isocitrate dehydrogenase.

Next, α-ketoglutarate dehydrogenase decarboxylates and oxidizes α-ketoglutarate in the presence of coenzyme A to form succinyl-CoA.

In the fifth step, succinyl-CoA synthetase converts succinyl-CoA to succinate, releasing coenzyme A.

Further, succinate is oxidized to fumarate by succinate dehydrogenase.

Fumarase hydrates the double bond of fumarate in the seventh step to yield malate.

Finally, the malate dehydrogenase enzyme oxidizes malate, regenerating oxaloacetate for the next round of the cycle.