Oxidation of glucose involves following four distinct stages - glycolysis, oxidative decarboxylation of pyruvic acid, Krebs cycle and Electron transport chain. In the first three stages, the hydrogen acceptor Nicotinamide adenine dinucleotide - oxidized form (NAD+) and Flavin adenine dinucleotide - oxidized form (FAD+) are reduced to NADH2 and FADH2 respectively. Both the coenzymes, (NAD+) and (FAD+) act as hydrogen carriers from respiratory substrate to electron transport chain, where H+ and electrons are transferred to oxygen to form water. This electron transport results in the release of energy, which is used to phosphorylate ADP to ATP. Hence, the electron transport chain reactions are referred to as oxidative phosphorylation.
In 1937, Sir Hans Adolf Krebs described the catalytic role of pyruvic acid for the production of energy in the cell. The series of cyclic reactions involved in converting pyruvic acid to carbondioxide and water in mitochondria is called Krebs cycle. It is also known as citric acid cycle or tricarboxylic acid cycle - TCA cycle.
1. In the first reaction of citric acid cycle, one molecule of acetyl Co~A combines with oxaloacetic acid to form citric acid. This reaction is catalyzed by citric acid synthetase. Citric acid contains three carboxylic acid groups.
2. Citric acid is dehydrated to form cis-aconitic acid in the presence of aconitase
3. The same enzyme aconitase catalyzes the formation of isocitric acid from cis-aconitic acid by the addition of a molecule of water. Citric acid, cis-aconitic acid and isocitric acid contain three carboxylic acid groups.
4. The isocitric acid is oxidatively decarboxylated to a- ketoglutaric acid. This reaction is catalyzed by isocitric dehydrogenase. During this reaction, one NADH2 is formed.
5. The a- ketoglutaric acid is oxidatively decarboxylated to form succinyl Co~A. This reaction is catalyzed by a-ketoglutaric dehydrogenase. The energy released during this reaction is conserved in
6. The succinyl Co~A is hydrolysed to succinic acid in the presence of succinyl Co-A synthetase. In this reaction, ADP is phosphorylated to ATP. This is called substrate level phosphorylation.
7. The succinic acid is oxidized to form fumaric acid by succinic dehydrogenase. Here, FAD+ is reduced to FADH2.
8. The fumaric acid is converted to malic acid by the addition of a molecule of water. This reaction is catalyzed by fumarase.
9. The malic acid is oxidized to oxaloacetic acid by the enzyme malic dehydrogenase. Here, NAD+ is reduced to NADH2.
2 molecules of acetyl CoA enter into Krebs cycle which on subsequent oxidation generate 6NADH2, 2FADH2.. When 6NADH2, 2FADH2 enter into the electron transport system generate 22ATP molecules. In one step, there is substrate level phosphorylation whch directly yield 2ATP molecules. So, during Krebs cycle, every 2 molecules of acetyl CoA enter into Krebs cycle 24 ATP molecules are generated. So, primarily it is a energy producing system. Since, Krebs cycle involves with both anabolic and catabolic processes, it is also described as amphibolic process.