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Monday, September 19, 2011

Krebs cycle (reactions) - part 2

Reaction 5: conversion of succinyl-CoA to succinate This reaction requires Mg2+. The enzyme that catalyzes this reaction, succinyl-CoA synthetase, breaks the thioester bond (S-CoA), releasing a large amount of energy that is used to phosphorylate GDP to GTP. It is another example of an energy coupling.








Reaction 6: oxidation of succinate to fumarate
Succinate is oxidized to fumarate, leading to the production of FADH2 from FAD. The reaction is catalyzed by succinate dehydrogenase, which is the only Krebs cycle enzyme that is not present in the matrix, but instead is strongly associated with the inner membrane of mitochondria.











Step 7: Hydration of fumarate to malate
This enzyme is highly stereo-specific, producing only the stereoisomer L-malate. The reaction is reversible in cellular conditions.



Step 8: oxidation of malate to oxaloacetate
This reaction produces a molecule of NADH from NAD+. At the intracellular conditions, the reaction is mainly driven in the opposite direction, but as the oxaloacetate is continuously removed (by the reaction of synthesis of citrate, by gluconeogenesis or by transamination to originate aspartate), the equilibrium is shifted in the forward direction. The oxaloacetate used in the first reaction of the Krebs cycle is then regenerated, so, theoretically, one molecule of oxaloacetate may be involved in the oxidation of an infinite number of molecules of acetyl-CoA (playing a kind of "catalytic" role) and, therefore, the oxaloacetate is present in cells at very low concentrations.
  
Main bibliographic sources:
- Quintas A, Freire AP, Halpern MJ, Bioquímica - Organização Molecular da Vida, Lidel
- Nelson DL, Cox MM, Lehninger - Principles of Biochemistry, WH Freeman Publishers

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