Glycolysis results in pyruvate. Based on the availability of oxygen, pyruvate either undergoes anaerobic or aerobic respiration.
Aerobic respiration involves the transport of pyruvate from cytoplasm into the mitochondria for complete oxidation in Krebs’ cycle. It also involves the transfer of hydrogen ions and electrons from the co-enzymes, NADH + H+ and FADH2, to oxygen in the electron transport system, for ATP synthesis. Inside the mitochondria, the pyruvate undergoes oxidative decarboxylation in the presence of the pyruvate dehydrogenase enzyme, NAD+, and co-enzyme A. The NAD+ is reduced to NADH + H+, and co-enzyme A combines with the acetyl group of pyruvate to form acetyl CoA.
The acetyl CoA thus formed enters Krebs’ cycle, which has been named after the scientist, Sir Hans Adolf Krebs. Krebs’ cycle starts with the reaction of acetyl CoA with oxaloacetic acid to form citric acid catalysed by the enzyme, citrate synthase, with the release of co-enzyme A. The citric acid thus formed isomerises to form isocitric acid. The isocitric acid is then oxidised, which is later decarboxylated to form α-ketoglutaric acid. This α-ketoglutaric acid undergoes oxidative decarboxylation using co-enzyme A to form succinyl-CoA along with the reduction of NAD+ to NADH + H+ ion. The succinyl CoA formed is hydrolysed to succinic acid with the release of co-enzyme A. This reaction also results in the production of GTP.
The GTP thus formed is again converted back into GDP coupled with the synthesis of ATP from ADP. The succinic acid formed in the previous reaction is oxidised to fumaric acid with the reduction of FAD+ to FADH2. The fumaric acid is hydrolysed to malic acid, which is then oxidised to oxaloacetic acid with the reduction of NAD+ to NADH + H+ ion.
For Krebs’ cycle to run continuously, oxaloacetic acid, NAD+ and FAD+ need to be regenerated. The net gain of Krebs’ cycle in the conversion of two molecules of pyruvate is 2 molecules of ATP, 8 molecules of NADH + H+ and 2 molecules of FADH2. So far, the energy harvested has resulted in the direct synthesis of only 4 molecules of ATP. Further generation of energy as part of aerobic respiration takes place in the electron transport system.