KREB'S CYCLE

 KREB’S CYCLE

• The Kreb’s cycle (Citric acid cycle or Tricarboxylic acid - TCA cycle) is the most important metabolic pathway for the energy supply to the body. About 65 – 70 % of the ATP is synthesized in Kreb’s cycle. Citric acid cycle essentially involves the oxidation of Acetyl CoA to CO₂ and H₂O.
• The name TCA cycle is used, since, at the outset of the cycle, Tricarboxylic acids (Citrate, cis-aconitate and Isocitrate) participate.
• The Citric acid cycle was proposed by Hans Adolf Krebs in 1937, based on the studies of Oxygen consumption in pigeon breast muscle. The cycle is named in his honour (Nobel Prize for Physiology and Medicine in 1953).
• The enzymes of TCA cycle are located in Mitochondrial matrix, in close proximity to the Electron transport chain. This enables the synthesis of ATP by Oxidative phosphorylation without any hindrance.
• The Citric acid cycle is the final common Oxidative pathway for carbohydrates, fats and amino acids. This cycle not only supplies energy but also provides many intermediates required for the synthesis of Amino acids, Glucose, Heme, Nucleotides (Purines & Pyrimidines), etc. Krebs cycle is the most important central pathway connecting almost all the individual metabolic pathways.
• Kreb’s cycle is a cyclic process.
• Kreb’s cycle is called as Amphibolic in nature because it has dual role Catabolism and Anabolism.  Catabolic role – The two carbon compound Acetyl – CoA produced from metabolism of Carbohydrates, Lipids and Proteins are oxidized in this cycle to produce CO₂, H₂O and energy as ATP. Anabolic role - Intermediates of TCA cycle are utilized for synthesis of various compounds like Amino acids, Glucose, Heme, Nucleotides (Purines & Pyrimidines), etc.

Kreb’s cycle or Citric acid cycle or TCA cycle

• Step – 1: A turn of the cycle begins as enzymes strip off the CoA portion from Acetyl CoA and combine the remaining two - carbon acetyl group with Oxaloacetic acid. Adding the acetyl group produces the six-carbon molecule Citric acid.
• Step – 2 to Step – 4: Oxidations generate NADH. Step 2 is a rearrangement. Steps 3 and 4 combine Oxidations and Decarboxylations to dispose of two carbon atoms that came from Oxaloacetic acid. The carbons are released as CO₂, and the oxidations generate NADH from NAD⁺. During the second oxidation (step 4), CoA is added into the cycle, forming the compound Succinyl CoA.
• Step – 5: ATP is produced by Substrate level phosphorylation. CoA is removed from Succinyl CoA, leaving Succinic acid.
• Step – 6: Enzymes rearrange chemical bonds, producing three different molecules before regenerating Oxaloacetic acid. In Step 6, an oxidation produces FADH₂. In Step 8, a final oxidation generates NADH and converts Malic acid to Oxaloacetic acid, which is ready to enter another round of the Krebs cycle.