The Krebs cycle is an aerobic cycle of breaking down acetyl CoA. Each cycle yields a molecule of FADH₂ (flavin adenine dinucleotide+ H₂), a molecule of GTP (guanosine triphosphate), three molecules of NADH (nicotinamide adenine dinucleotide + hydrogen) , and two molecules of carbon dioxide. The aerobic breakdown of pyruvate (final product of glycolysis), beta oxidation of fatty acids, and catabolism of amino acids results in the formation of acetyl CoA. Krebs cycle occurs inside the mitochondrial matrix of the eukaryotic cell and in the cytoplasm of prokaryotic cells.
Krebs cycle is also known as the TCA (Tricarboxylic acid) cycle or citric acid cycle because citric acid is produced in the first step which has 3 carboxyl (-COOH) groups.
Steps of Krebs Cycle
- Firstly there is the formation of six-carbon compound-citrate by combining Acetyl CoA and oxaloacetate. The enzyme required is citrate synthase
- Secondly, there is the conversion of citrate to its isomer isocitrate in the presence of the enzyme aconitase.
- Thirdly, the isocitrate converts into ɑ-ketoglutarate. A molecule of carbon dioxide releases in this step because ɑ-ketoglutarate is a 5-carbon compound. The catalyst of this step is NAD and isocitrate dehydrogenase.
- Then, the four-carbon compound succinyl CoA forms under the control of the enzyme ɑ-ketoglutarate dehydrogenase—a molecule of carbon dioxide and NADH forms in this step.
- Fifthly, this step involves the removal of CoA from succinyl CoA to form succinate. GTP forms in this method. The catalyst is succinyl CoA synthetase.
- Similarly, in this step, the succinate converts into fumarate. The enzyme succinate dehydrogenase helps the reaction. The succinate dehydrogenase reduces FAD to FADH₂.
- Likewise, with the addition of H₂O, the fumarate changes into malate. The presence of fumarase in this step acts as a catalyst.
- The final step is the formation of oxaloacetate with the help of the enzyme malate dehydrogenase.
Krebs cycle is amphibolic; catabolism (breakdown) and anabolism (synthesis) co-occur.
- NADH inhibits almost all the enzymes of TCA, and FADH₂ inhibits succinate dehydrogenase.
- The citrate inhibits phosphofructokinase, an essential enzyme of glycolysis. It controls the production of pyruvate.
- Whereas Calcium ions accelerate the TCA cycle.
- Rate of conversion of pyruvate to acetyl Coenzyme A.
Products of Krebs Cycle
A molecule of acetyl CoA gives following products:
- Carbon dioxide: In addition to the third and the fourth steps produce one carbon dioxide molecule each.
- NADH: The third, fourth, and last steps of the cycle produce three NADH molecules.
- GTP: A molecule of GTP forms in the fifth step of the process.
- Hydrogen ions: Three molecules of hydrogen ions are released in the third, fourth, and last steps of the cycle.
- FADH₂: A molecule of FADH₂ is produced in the sixth step.
From the process of oxidative phosphorylation a molecule FADH₂ produces 1.5 ATP and a molecule of NADH produces 2.5 ATP. So, Krebs cycle produce almost 10 ATP from a molecule of acetyl CoA.
Reference and Further Reading
- Nelson, D., Lehninger, A., Cox, M., & Nelson, D. (2005). Lecture notebook for Lehninger principles of biochemistry, fourth edition (pp. 601-612). W.H. Freeman.
- Rodwell, V., Bender, D., Botham, K., Kennelly, P., & Weil, P. (2015). Harper’s illustrated biochemistry (30th ed., pp. 161-167). McGraw Hill.
- (2022). Retrieved 2 May 2022, from https://teachmephysiology.com/biochemistry/atp-production/tca-cycle-2/.
- tricarboxylic acid cycle | biochemistry. Encyclopedia Britannica. (2022). Retrieved 2 May 2022, from https://www.britannica.com/science/tricarboxylic-acid-cycle.