Citric acid cycle

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The Citric Acid Cycle, also called Krebs cycle, Citrate Cycle, or TCA (Tricarboxylic Acid Cycle) is a series of chemical reactions that occur in living cells and metabolize (break down and convert) carbohydrates (simple sugars,e.g., glucose) to energy, carbon dioxide and water. It is named after Sir Hans Adolf Krebs (1900-1981), who was awarded the 1953 Nobel Prize in Medicine for the discovery of this metabolic pathway. The Krebs cycle is localized within the mitochondria in eukaryotes, and within the cytoplasm in prokaryotes. It is part of the metabolic pathway in aerobic organisms (uitlizing oxygen as part of cellular respiration);anaerobic organisms use other mechanisms, such as glycolysis and other oxygen-independent fermentation processes.

The Krebs cycle is the second of three steps in carbohydrate catabolism (the breakdown of carbon-containing compounds), between glycolysis and oxidative phosphorylation. Citrate is both the first and last product of the cycle (Fig. 1), and is regenerated by the condensation of oxaloacetate and acetyl-CoA, the latter being a result of a prior breakdown process, e.g., glycolysis (in glycolysis, glucose (a six-carbon-molecule) is broken down to pyruvate (a three-carbon-molecule), prior to cellular respiration), protein catabolism (Proteins are broken down outside the cells by protease enzymes. The amino acids are brought inside the cells and funnel into glycolysis or the Krebs cycle.) or fat catabolism(Triglycerides/triacylglycerols are hydrolyzed (hydrogen molecules are added) to break them into fatty acids and glycerol. The glycerol is then converted into glyceraldehyde-3-phosphate, which goes through the process known as hydrolysis. Fats that are to be catabolized go through a process known as beta oxidation (the oxidation of beta particles). Beta oxidation breaks down fatty acids into two carbon molecules (Acetyl-CoA). The two carbons are then catabolized in the Krebs cycle.) (Fig. 2).


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Figure 1 : Schematic drawing of the Krebs cycle.

Molecule Enzyme Reaction Type Reactants/
Coenzymes
Products/
Coenzymes
I. Citrate 1. Aconitase Dehydration    H2O
II. cis-Aconitate 2. Aconitase Hydration H2O   
III. Isocitrate 3. Isocitrate Dehydrogenase Oxidation NAD+ NADH+H+
IV. Oxalosuccinate 4. Isocitrate Dehydrogenase Decarboxylation      
V. α-Ketoglutarate 5. α-Ketoglutarate Dehydrogenase Oxidative Decarboxylation NAD+
CoA-SH
NADH+H+
CO2
VI. Succinyl-CoA 6. Succinyl-CoA Synthetase Hydrolysis GDP
Pi
GTP
CoA-SH
VII. Succinate 7. Succinate Dehydrogenase Oxidation FAD+ FADH2
VIII. Fumarate 8. Fumerase Addition (H2O) H2O   
IX. L-Malate 9. Malate Dehydrogenase Oxidation NAD+ NADH+H+
X. Oxaloacetate 10. Citrate Synthetase Condensation      
XI. Acetyl-CoA            

The sum of all reactions in the Krebs cycle is :

Acetyl-CoA-SH+3NAD++FAD++ADP+Pi ==> CoA-SH+3NADH+H++FADH2+ATP+2CO2

Two carbons are oxidized to CO2, and the energy from these reactions are stored in ATP(ATP is the "universal energy currency" of the cell), NADH and FADH2. NADH and FADH2 are coenzymes (Coenzymes are molecules that enable or enhance enzymes.) that store energy and can release it when needed. The total energy gained by the Krebs cycle equals 2 ATP, the total energy gained from all from all four processes in cellular respiration equals 38 ATP, generated from each molecule of glucose.

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Figure 2 : Schematic drawing of metabolic pathways associated with the Krebs cycle.

  1. Protein catabolism.
  2. Fat catabolism.
  3. Carbohydrates.
  4. Amino Acids.
  5. Acetyl-CoA.
  6. Pyruvate.
  7. Krebs Cycle.


See also biochemistry.


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