TCA CyclE

TCA Cycle Overview

• Also known as Kreb's cycle or Citric acid cycle
• Final common oxidative pathway for carbohydrates, fats, and amino acids
• Supplies energy and many intermediates for amino acid, glucose, and heme synthesis
• Located in the mitochondrial matrix
• Involves the oxidation of acetyl CoA to CO2 and H2O in a cyclic manner, generating ATP

Reactions of TCA Cycle

• Acetyl CoA + Oxaloacetate → Citrate
• Isocitrate → Oxalosuccinate → α-Ketoglutarate
• α-Ketoglutarate → CO2 and NADH
• Oxidation of acetyl CoA → CO2 and H2O

Energetics of TCA Cycle

• Steps 4, 6, 10: 3 NADH = 9 ATP
• Step 8: 1 FADH2 = 2 ATP
• Step 7: 1 GTP = 1 ATP
• Total ATP yield per acetyl CoA: 12 ATP
• Total ATP yield per glucose: 38 ATP

Amphibolic Nature of TCA Cycle

• Both catabolic and anabolic
• Intermediates are used for amino acid, glucose, and heme synthesis
• Examples of amphibolic reactions:
  • Aspartate and purine synthesis from oxaloacetate
  • Fatty acid and steroid synthesis from acetyl CoA
  • α-Ketoglutarate and glutamate synthesis from transamination

Anaplerotic Reactions

• Replenish TCA cycle intermediates
• Examples:
  • Pyruvate + CO2 + ATP → Oxaloacetate + ADP + Pi
  • Pyruvate + CO2 + NADPH + H+ → Malate

Inhibitors of TCA Cycle Enzymes

• Aconitase inhibited by fluoroacetate
• α-Ketoglutarate dehydrogenase inhibited by arsenite
• Succinate dehydrogenase inhibited by malonate

Regulation of TCA Cycle

• Citrate synthase inhibited by ATP, NADH, acyl CoA, and succinyl CoA

Test your understanding of the tricarboxylic acid cycle (TCA cycle), also known as Kreb's cycle or citric acid cycle, and its role in energy production and synthesis of amino acids, glucose, and heme. Calculate the energy yield per turn of the cycle and describe the further processing of acetyl-CoA.