Krebs Cycle

• In 1937, Sir Hans Krebs, discovered series of metabolic reactions that became known as Krebs Cycle. He received the Nobel Prize in 1953 for this important discovery 

• Fritz Albert Lipmann shared the Nobel Prize with Krebs for his discovery of coenzyme A and the key role it plays in metabolism

• Krebs cycle is a cyclic series of reactions that transfer energy from organic molecules to ATP, NADH, and FADH2 and removes carbon atoms as CO2
• Krebs cycle is an eight-step process, each step catalyzed by a specific enzyme.

• Krebs cycle is a cyclic process because oxaloacetate, product of step eight is the reactant in step one.
• The overall chemical equation for Krebs cycle is:

oxaloacetate+acetyl-CoA+ADP+Pi+3NAD+FAD---->

CoA+ATP+3NADH+3H+FADH2+CO2

• The Krebs cycle begins as acetyl-CoA condenses with oxaloacetate to form citrate. 

• In glycolysis, glucose is broken down into two pyruvate molecules. 2-carbon fragment of pyruvate is used in making acetyl-CoA. Acetyl-CoA enters the kreb cycle, which takes place in mitochondrion.
• In the process of converting pyruvate into acetyl-CoA, CO2 is produced and a molecule of NADH is formed.
• The acetyl group (2-C) of acetyl-CoA is transferred to a 4-C molecule, which will produce 6-C compound. CoA is released.
• The 6-C molecule is then converted into a 5-C compound by loosing CO2 and 2 H atoms that reduce NAD+ to NADH.
• Oxidation and decarboxylation occurs. NADH and CO2 are produced. ATP is produced as well. As a result of these reactions, 4-C molecule is formed
• 4-C molecule is further oxidized and hydrogens that were removed are used in making NADH and FADH2. These reactions regenerate the 4-C molecule that reacted with acetyl-CoA.
• By the end of Krebs cycle the glucose molecule is entirely consumed. The 6-C atoms leave the process as 6 low energy CO2 molecules, which are released as wastes.
• In one turn of the cycle, the last 2-C atoms of the original glucose molecule are removed as CO2 , and free energy is transferred to ATP, NADH and  FADH2
• All that is preserved of the original glucose molecule is mostof its energy which is stored as: 4 ATP molecules (2 from glycolysis and 2 from Krebs cycle) and 12 reduced coenzymes ( 2 NADH from glycolysis, 2 NADH from pyruvate oxidation, 6 NADH from Krebs cycle and 2 FADH2 from the Krebs cycle)
• Free energy stored in NADH and FADH2 will eventually be transferred to ATP in the last stage of cellular respiration, called the electron transport and chemiosmosis
• The Krebs cycle occurs twice for each molecule of glucose processed, since 2 molecules of acetyl-CoA are formed from one molecule of glucose
• By the end of Krebs cycle, all 6-C atoms of glucose have been oxidized to CO2 and released from the cell as metabolic waste
• The reduced coenzymes, NADH and FADH2 now go on to the next process, electron transport and chemiosmosis, where their free energy will be transferred to ATP