TCA Cycle

TCA Cycle (Krebs / Citric Acid Cycle)

The TCA cycle is a circular series of 8 reactions occurring in the mitochondrial matrix. It is the final common pathway for the oxidation of carbohydrates, fats, and amino acids. Each turn completely oxidizes one acetyl group (2 carbons) to 2 CO₂.

Entry Point

Acetyl-CoA (2C) condenses with Oxaloacetate (4C) to form Citrate (6C) — catalyzed by Citrate Synthase. The 2 carbons from acetyl-CoA are not lost until the 2nd turn (equivalent carbons are released as CO₂).

8 Steps of TCA Cycle

  1. Citrate Synthase: OAA + Acetyl-CoA → Citrate (irreversible; inhibited by NADH, succinyl-CoA, ATP)
  2. Aconitase: Citrate → Isocitrate (via cis-Aconitate); inhibited by fluoroacetate
  3. Isocitrate Dehydrogenase: Isocitrate → α-Ketoglutarate + CO₂ + NADH (rate-limiting step; activated by ADP; inhibited by NADH, ATP)
  4. α-Ketoglutarate Dehydrogenase: α-KG → Succinyl-CoA + CO₂ + NADH (requires TPP, FAD, NAD+, CoA, lipoic acid — same as PDC)
  5. Succinyl-CoA Synthetase: Succinyl-CoA → Succinate + GTP (only substrate-level phosphorylation in TCA)
  6. Succinate Dehydrogenase: Succinate → Fumarate + FADH₂ (Complex II of ETC; inhibited by malonate)
  7. Fumarase: Fumarate → Malate (hydration)
  8. Malate Dehydrogenase: Malate → Oxaloacetate + NADH (regenerates OAA to continue cycle)

Energy Yield per Acetyl-CoA

  • 3 NADH → 7.5 ATP (via ETC)
  • 1 FADH₂ → 1.5 ATP (via ETC)
  • 1 GTP → 1 ATP
  • Total: ~10 ATP per acetyl-CoA
  • Per glucose (2 acetyl-CoA): ~20 ATP from TCA alone

Amphibolic Nature

TCA is amphibolic — serves both catabolism AND anabolism. Intermediates are withdrawn (cataplerosis) for biosynthesis: α-KG → glutamate/GABA; OAA → aspartate/glucose; Succinyl-CoA → heme synthesis; Citrate → fatty acid synthesis (exits mitochondria).

Anaplerotic Reactions (refilling TCA)

  • Pyruvate Carboxylase: Pyruvate + CO₂ → OAA (activated by Acetyl-CoA; requires Biotin). Major anaplerotic reaction in liver.
  • Amino acid catabolism → α-KG, OAA, succinyl-CoA, fumarate, malate
  • Propionyl-CoA (odd-chain FA) → Succinyl-CoA

Regulation

TCA is regulated by: substrate availability, product inhibition (NADH, ATP inhibit key enzymes), and calcium (activates isocitrate dehydrogenase, α-KGDH, and PDC in muscle — coupling contraction with energy production).

Quiz - Exam Preparation Strategy

When studying Quiz for your final board exams, it is critical to focus on the core concepts and fundamental formulas. Relying strictly on NCERT textbook solutions and practicing previous year questions (PYQs) is the proven methodology for scoring high marks. Avoid rote memorization and instead focus on the logical application of the theories presented in this chapter.

⚠️ Common Mistakes to Avoid

❓ Frequently Asked Questions

How can I quickly memorize the concepts of Quiz?

The most effective way is to create short, handwritten revision notes and continuously test your knowledge using our interactive Mock Tests. Spaced repetition and active recall are much better than passive reading.

What type of questions are most commonly asked from Quiz?

Board exams tend to favor conceptual application questions and direct formula-based derivations from the NCERT syllabus. Ensure you have solved every single exercise in the official textbook.

Is reading the NCERT book enough for this chapter?

Yes, the NCERT textbook is the absolute gold standard for board exams. However, to improve your speed and accuracy during the actual exam, you must supplement your reading by solving timed mock tests and objective questions.