TRICARBOXYLIC ACID CYCLE (TCA CYCLE)

BCK - schema Cycle de Krebs v2-02

Glycolysis that generates pyruvate is linked to the tricarboxylic acid cycle (TCA cycle also named citric acid cycle or Krebs cycle), that takes place within mitochondria, is a series of enzyme-catalyzed chemical reactions that form a key part of aerobic respiration in cells and is central to the regulation of energy homeostasis and cell metabolism. It is the gateway to the aerobic metabolism of any molecule (glucid, lipid, protein) that can be transformed into an acetyl group or a dicarboxylic acid.

At the beginning, pyruvate enters the mitochondria and is oxidized by pyruvate dehydrogenase (PDH) in acetylCoA. Then, a four-carbon compound (oxaloacetate) condenses with a two-carbon acetyl unit (acetylcoA) to yield free CoA and a six-carbon tricarboxylic acid (citrate), a reaction catalyzed by citrate synthase (CS). Then, citric acid goes through a number of steps and then recombines with acetyl CoA to make more citric acid which goes through the same cycle of steps again. Carbon dioxide is formed at two of the steps in this process and hydrogen atoms are removed from the molecules along with their electrons at four of them. After isomerisation of citrate into isocitrate by aconitase, isocitrate is then oxidatively decarboxylated by isocitrate dehydrogenase (IDH). Electrons are removed and transferred to NAD to form NADH and carbon dioxide released. The resulting five-carbon compound (α-ketoglutarate) is then oxidatively decarboxylated by α-ketoglutarate dehydrogenase (KDH) generating NADH, the last carbon dioxide molecule and a four-carbon compound (succinate). As the formation of succinate from α-ketoglutarate is very exergonic (more than is needed to make NADH), the excess energy is conserved by the addition of CoA to the succinate thus forming succinyl-CoA. The energy that was stored in the linkage of the CoA to succinate is now used to attach a phosphate to GDP to form GTP. By the action of succinylcoA synthetase, CoA is removed and succinate is formed. Then succinate is oxidized to fumarate by succinate dehydrogenase (SDH), FAD being the electron acceptor and forming FADH2. Next oxidation reaction that produces an NADH converts fumarate to malate by fumarase. Oxaloacetate is then regenerated from succinate.