11 Questions
What is the end product of the oxidation of acetyl CoA in the TCA cycle?
CO2 + H2O
What is the site of the TCA cycle?
Mitochondrial matrix
What is the immediate product of the reaction between acetyl CoA and oxaloacetate?
Citrate
What is the significance of the TCA cycle in the synthesis of biomolecules?
It supplies many intermediates required for the synthesis of amino acids, glucose, and heme
What is the fate of cis-aconitate in the TCA cycle?
Immediate H2O is added to it to form isocitrate
What is the net gain of ATP during the complete oxidation of glucose?
38 ATP
What is the product of the spontaneous decarboxylation of oxalosuccinate?
α-KG
What is the role of malic enzyme in anaplerotic reactions?
Converting pyruvate to malate
What is the effect of arsenite on the TCA cycle?
Non-competitive inhibition of α-ketoglutarate dehydrogenase
What is the purpose of anaplerotic reactions in the TCA cycle?
To replenish intermediates of the TCA cycle
What is the effect of ATP on citrate synthase?
Inhibition
Study Notes
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.
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