Monday, August 29, 2011

Krebs cycle (general ideas) - part 2

For each round of the Krebs cycle, three molecules of NADH, 1 FADH2, 1 ATP (GTP) are produced.

The passage of electrons from a molecule of NADH to O2 on oxidative phosphorylation leads to the formation of 2.5 molecules of ATP. If the donor electron is the FADH2 only 1.5 molecules of ATP are formed. Therefore, one molecule of glucose that is completely oxidized to CO2 via glycolysis, pyruvate dehydrogenase, Krebs cycle and oxidative phosphorylation, produces 32 ATP molecules.

The Krebs cycle plays a central role in cellular metabolism, because all the nutrients that may play a role "energy" generated in its catabolism acetyl-CoA.In addition to oxidize acetyl-CoA to CO2 and to produce ATP, NADH and FADH2, also receives several intermediaries arising from several catabolic pathways. Oxaloacetate and α-ketoglutarate, for example, are the products of decomposition of aspartate and glutamate. In addition to receiving several intermediates from catabolic processes, it also provides various intermediates for anabolic pathways. Because of this feature (involvement on both anabolic and catabolic processes) the Krebs cycle is an amphibolic process.
Oxaloacetate and α-ketoglutarate are also precursors of amino acids and purine and pyrimidine bases. Oxaloacetate is converted to glucose in gluconeogenesis, succinyl-CoA intermediate in the synthesis of the porphyrin ring of heme groups.
When the Krebs cycle intermediates are diverted to biosynthetic processes, their stock quantity is replenished by anaplerotic reactions. The most important reaction in the liver and kidneys is the reversible carboxylation of pyruvate to oxaloacetate. The enzyme that catalyzes this reaction is pyruvate carboxylase and is stimulated by acetyl-CoA. Another important reaction is the carboxylation of phosphoenolpyruvate to oxaloacetate. The enzyme that catalyzes this reaction is phosphoenolpyruvate and is stimulated by fructose-1,6-bisphosphate. Other important anaplerotic reactions are transaminations, to obtain amino acids (the intermediate of cycle provides the carbon skeleton). The cycle also provides intermediates in the synthesis of glucose (gluconeogenesis) and fatty acids.

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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