The 8 Powerful Enzymes of Kreb Cycle, TCA Cycle or Citric Acid Cycle

Kreb cycle pathway showing kreb cycle enzymes in the process

 Kreb cycle enzymes, TCA enzymes or enzymes of citric acid cycle are the enzymes involved in the kreb Cycle pathway. This pathway consumes acetyl CoA to yield energy.

Kreb Cycle citric acid cycle, also known as the Krebs cycle or tricarboxylic acid (TCA) cycle, is the second stage of cellular respiration. The first stage of cellular respiration is Glycolysis.  This cycle is catalyzed by several enzymes and is named in honor of the British scientist Hans Krebs who identified the series of steps involved in the citric acid cycle.

The usable energy found in the carbohydrates, proteins, and fats we eat is released mainly through the citric acid cycle. Although the citric acid cycle does not use oxygen directly, it works only when oxygen is present.

Key Notes

  • The second stage of cellular respiration is called the citric acid cycle. It is also known as the Krebs cycle after Sir Hans Adolf Krebs who discovered its steps.
  • Kreb Cycle Enzymes play an important role in the citric acid cycle. Each step is catalyzed by a very specific enzyme.
  • In eukaryotes, the Krebs cycle uses a molecule of acetyl CoA to generate 1 ATP, 3 NADH, 1 FADH2, 2 CO2, and 3 H+.
  • Two molecules of acetyl CoA are produced in glycolysis so the total number of molecules produced in the citric acid cycle is doubled (2 ATP, 6 NADH, 2 FADH2, 4 CO2, and 6 H+).
  • Both the NADH and FADH2 molecules made in the Krebs cycle are sent to the electron transport chain, the last stage of cellular respiration.

The first phase of cellular respiration, called glycolysis,‚Äč takes place in the cytosol of the cell’s cytoplasm. The citric acid cycle, however, occurs in the matrix of cell mitochondria. Prior to the beginning of the citric acid cycle, pyruvic acid or pyruvate generated in glycolysis. It will be transported across the mitochondrial membrane and is used to form acetyl coenzyme A (acetyl CoA). Acetyl CoA is then used in the first step of the citric acid cycle. Each step in the cycle is catalyzed by a specific enzyme.

Citrate synthase 

The two-carbon acetyl group of acetyl CoA will diffused with the four-carbon oxaloacetate to form the six-carbon citrate. The citric acid cycle enzymes that pilots this reaction is citrate synthase. The conjugate acid of citrate is citric acid, hence the name citric acid cycle.

Oxaloacetate is regenerated at the end of the cycle so that the cycle may continue. The pathway consumes the acetyl molecules that diffuse with oxaloacetate. The oxaloacetate will be regenerated and start another sequence of the chain reaction.


These Kreb cycle enzymes function in the reaction where citrate loses a molecule of water and another is added. In the process, citric acid is converted to its isomer isocitrate. We can say that the enzyme is a hydratase.

Isocitrate Dehydrogenase

Isocitrate loses a molecule of carbon dioxide (CO2) and is oxidized forming the five-carbon alpha ketoglutarate. Nicotinamide adenine dinucleotide (NAD+) is reduced to NADH + H+ in the process. The process of loosing the carbon dioxide it known as decarboxylation. NADH2 is further used to generate energy in electron transport chain. This TCA cycle enzymes undergo both dehydrogenation and decarboxylation.

Alpha Ketoglutarate Dehydrogenase

Alpha ketoglutarate is converted to the 4-carbon succinyl CoA. A molecule of CO2 is removed and NAD+ is reduced to NADH + H+ in the process. This enzymes of citric acid cycle removes of strips Hydrogen off the substrate.

Succinyl-CoA Synthetase

CoA is removed from the succinyl CoA molecule and is replaced by a phosphate group. The phosphate group is then removed and attached to guanosine diphosphate (GDP) thereby forming guanosine triphosphate (GTP). Like ATP, GTP is an energy-yielding molecule and is used to generate ATP when it donates a phosphate group to ADP. The final product from the removal of CoA from succinyl CoA is succinate.

Succinate Dehydrogenase

This TCA Cycle enzymes is involved in the reaction where Succinate is oxidized and converted to fumarate. Flavin adenine dinucleotide (FAD) is reduced and forms FADH2 in the process.


This kreb Cycle enzymes functions when a water molecule is added and bonds between the carbons in fumarate are rearranged, thus forming malate.

Malate Dehydrogenase

Malate is oxidized forming oxaloacetate, the beginning substrate in the cycle. NAD+ is reduced to NADH + H+ in the process. This Kreb Cycle enzymes marks the end of one turn of the cycle.

For the proper understanding of the steps of the pathway, check our article on Krebs cycle.

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Sir Hans Adolf Krebs

Sir Hans Adolf Krebs (1900-1981), British biochemist who discovered the citric acid cycle (Krebs cycle). He won the Nobel Prize for physiology in 1953.Bettmann / Contributor / Bettmann / Getty Images

In eukaryotic cells, the citric acid cycle uses one molecule of acetyl CoA to generate 1 ATP, 3 NADH, 1 FADH2, 2 CO2, and 3 H+. Since two acetyl CoA molecules are generated from the two pyruvic acid molecules produced in glycolysis, the total number of these molecules yielded in the citric acid cycle is doubled to 2 ATP, 6 NADH, 2 FADH2, 4 CO2, and 6 H+. Two additional NADH molecules are also generated in the conversion of pyruvic acid to acetyl CoA prior to the start of the cycle. The NADH and FADH2 molecules produced in the citric acid cycle are passed along to the final phase of cellular respiration called the electron transport chain. Here NADH and FADH2 undergo oxidative phosphorylation to generate more ATP.

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