Citric Acid Cycle
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The citric acid cycle (TCA cycle) occurs in the mitochondria and involves a series of reactions that oxidize acetyl groups from acetyl-CoA derived from carbohydrates, fats, and proteins, releasing carbon dioxide and reducing equivalents (NADH and FADH2) that are used to generate ATP through oxidative phosphorylation. The TCA cycle produces two GTP/ATP molecules per acetyl-CoA molecule oxidized and feeds reduced electron carriers into the electron transport chain to produce additional ATP. It is also an amphibolic pathway that generates precursors for various biosynthetic pathways.
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Citric Acid Cycle
- 2. Other names- Krebs cycle, Tricarboxylic acid cycle Definition- It is a series of reactions in mitochondria that oxidize acetyl residues (as acetyl-CoA) librating reducing equivalents, which upon oxidation through ETC generate ATP. Site- Mitochondrial matrix
- 4. Oxaloacetate Acetyl-CoA Citrate Synthase CoA-SH Citrate Cis-aconitate Aconitase H2O H2O Isocitrate Oxalosuccinate Aconitase Fe++ H2O Isocitrate dehydrogenase NAD+ NADH+H+ α-Ketoglutarate Isocitrate dehydrogenase CO2 α-Ketoglutarate dehydrogenase NAD+ NADH+H+ CO2 CoA-SH Succinyl-CoA Succinate thiokinase ATP ADP + Pi Succinate CoA-SH Fumarate Succinate dehydrogenase FAD FADH2 L-Malate Fumarase H2O Malate dehydrogenase NAD+ NADH+H+ ETC ETC ETC ETC ATP Energetic of Citric Acid Cycle
- 5. Oxaloacetate Acetyl-CoA Citrate Synthase CoA-SH Citrate Cis-aconitate Aconitase H2O H2O Isocitrate Oxalosuccinate Aconitase Fe++ H2O Isocitrate dehydrogenase NAD+ NADH+H+ α-Ketoglutarate Isocitrate dehydrogenase CO2 α-Ketoglutarate dehydrogenase Succinyl-CoA Succinate thiokinase ATP ADP + Pi Succinate CoA-SH Fumarate Succinate dehydrogenase FAD FADH2 L-Malate Fumarase H2O Malate dehydrogenase NAD+ NADH+H+ - - - Fluroacetate (Non Competitive inhibitor) Arsenate (Non Competitive inhibitor) Malonate (Competitive inhibitor) Inhibitors of Citric Acid Cycle
- 6. Energetic of Glycolysis & Citric Acid Cycle Energy yield (ATP)/glucose in glycolysis under aerobic condition. Rea. no.1(Hexokinase) -1ATP Rea. 3 (PFK) -1ATP Rea. 6 (G 3-PDH) +2.5x2=5 Rea. 7 (BPGK) + 1x2=2 Rea. 10 (PK) + 1x2=2 Total=9-2=7ATP Energy yield (ATP)/glucose in TCA. Isocitrate DH 2.5x2=5ATP Ketoglutarate DH 2.5x2=5ATP S. thiokinase 1x2=2ATP S. DH 1.5x2=3ATP Malate DH 2.5x2=5ATP Total=20ATP Net ATP generation in glycolysis 9-2 =7ATP ATP generation in PDH 2.5x2=5ATP ATP generation in Citric acid cycle 20ATP Net generation of ATP from one glucose mol. 32ATP
- 7. The primary function is to provide energy (ATP). It is the final common pathway for the oxidation of carbohydrate, lipids, and protein via acetyl CoA or intermediates of the cycle. Citric acid cycle is an amphibolic process i.e, it plays role in both oxidative (catabolic) and synthetic (anabolic) processes. E.g…. Gluconeogenesis Transamination Fatty acid synthesis and Porphyrin synthesis. Significance of Citric Acid Cycle
- 8. Acetyl-CoA Citrate Cis-aconitate Isocitrate Oxalosuccinate α-Ketoglutarate Isocitrate dehydrogenase α-Ketoglutarate dehydrogenase Succinyl-CoA Succinate CoA-SH Fumarate L-Malate Regulation of Citric Acid Cycle Citrate Synthase Pyruvate PDH ATP, NADH, Acetyl CoA Ca++ -+ - ATP, NADH, Succinyl CoA - + ATP, NADH ADP - Succinyl CoA
- 9. Certain intermediates of TCA, can be removed from cycle for the synthesis of many compounds Succinate for haem (Porphyrin) synthesis. α-ketoglutarate for glutamate, GABA. α-ketoglutarate & oxaloacetate for many amino acids. Because this rate of TCA would expected to decline. However, intermediates of TCA can be replenished again by other reactions. The special enzyme reaction by which the pool of TCA intermediates can be replenished are called anaplerotic reactions. Anaplerotic reactions of Citric Acid Cycle
- 10. Acetyl-CoA Anaplerotic reactions of Citric Acid Cycle Oxaloacetate Citrate α-Ketoglutarate Succinyl-CoA Malate Fumarate AspartatePyruvate Glucogenic AA Pyruvate Valine isoleucine methionine threonine propionyl CoA Glutamate
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