Krebs Cycle
Overview
The Krebs cycle, also known as the citric acid cycle or the tricarboxylic acid cycle, is a series of chemical reactions used by all aerobic organisms to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins into adenosine triphosphate (ATP) and carbon dioxide.
History
The Krebs cycle was first postulated by the British scientist Sir Hans Adolf Krebs in 1937, for which he received the Nobel Prize in Physiology or Medicine in 1953.
Biochemical Function
The Krebs cycle is the second stage of cellular respiration, the first being glycolysis and the third being the electron transport chain. The cycle includes eight major steps. The cycle's Acetyl-CoA is synthesized in the mitochondria from food molecules and then combined with oxaloacetate to form citrate at the start of the cycle.
Steps of the Krebs Cycle
The eight steps of the Krebs cycle are as follows:
- Condensation: In the first step, the two-carbon acetyl group from acetyl-CoA combines with a four-carbon oxaloacetate molecule to form a six-carbon molecule of citrate.
- Isomerization: The citrate is rearranged to form an isomeric form called isocitrate.
- First Oxidation: Isocitrate is oxidized, producing a five-carbon molecule called alpha-ketoglutarate, and releasing one molecule of CO2 and reducing NAD+ to NADH.
- Second Oxidation: Alpha-ketoglutarate is oxidized, reducing NAD+ to NADH, releasing a molecule of CO2 and leaving a four-carbon molecule.
- Substrate-level Phosphorylation: The four-carbon molecule is rearranged, and a high-energy phosphate group is transferred to a molecule of GDP, forming GTP, which can be used to generate ATP.
- Third Oxidation: The four-carbon molecule is oxidized, reducing FAD to FADH2.
- Regeneration: The four-carbon molecule is further oxidized, reducing NAD+ to NADH.
- The oxaloacetate is now available to combine with another molecule of Acetyl-CoA and begin the cycle again.
Importance in Metabolism
The Krebs cycle plays a crucial role in the metabolic process. Its central importance lies in the energy that it provides to living cells. In addition, the cycle provides precursors of certain amino acids, as well as the reducing agent NADH, that are used in numerous other reactions.
Regulation
The Krebs cycle is regulated mainly by product inhibition and substrate availability. When the energy charge of the cell is high, the cycle is inhibited.