Abstrait

Two minutes and the two μM oxaloacetatemakes the phenotypic differences betweenproliferative and differentiation and the metastatic cells escape acidic microenvironment in search of a new life

Vadlakonda Lakshmipathi

Present model of intermediary metabolism has its origins in the first quarter of 20th century, developed by Meyerhof, who worked on muscles and Warburg on the cancers. Johnson and Krebs proposed the citric acid cycle, popularly known as the TCA cycle or Krebs cycle, when they observed that addition of small amounts of pyruvate increased the succinate levels in pigeon breast muscle extracts. They proposed the cyclic nature of the citric acid cycle based on two contemporary reports. Szent Gyorgyi reported that dicarboxylate oxidations supply hydrogens to oxygen to reduce it to water during the respiration. Martius group proposed that citric acid oxidation results in the production of the α-ketoglutarate (α-KG), but citric acid does not disappear from the reaction mixture. Besides, they proposed that the equilibrium of the first reaction, catalyzed by the aconitase favors the formation of 90% of citrate, and further proposed that isocitrate dehydrogenase (IDH) produces an intermediate oxalosuccinic acid, which is spontaneously decarboxylated to α-KG. Johnson in a later study confirmed that the equilibrium of aconitase reaction favors >80% of citrate formation. In extensive studies on citrate production, between 1945 -1960, Ochoa and his collaborators first proposed that citrate production involves the reductive carboxylation of the oxalosuccinate to citrate, and when the reaction is carried out in the presence of the glucose-6phosphate dehydrogenase (G6PDH) of the oxidative pentose phosphate pathway (oxPPP) and aconitase, Mg2+, and with NADPH as the cofactor, favors 90% citrate production.