Tricarboxylic Acid Cycle
ட்ரைகார்பாக்சிலிக் அமில சுழற்சி
Stop memorizing the TCA cycle as a list of names. It is the metabolic furnace of the cell, located strictly in the mitochondrial matrix. If you confuse the site of this cycle with the cytoplasm, you have already lost four marks.
The idea
The cycle begins with the condensation of Acetyl CoA (2C) with Oxaloacetic acid (4C) to form Citric acid (6C), catalyzed by citrate synthase. It involves two decarboxylation steps releasing CO2 and four oxidation steps. The process generates 3 NADH, 1 FADH2, and 1 GTP (ATP) per Acetyl CoA molecule. Remember, the cycle regenerates Oxaloacetic acid to continue the process.
Why it matters
It exists to completely oxidize the acetyl group derived from carbohydrates, fats, or proteins to harvest high-energy electrons for ATP synthesis.
NEET lens
NEET focuses on the input-output balance: 3 NADH, 1 FADH2, and 1 GTP per turn. Watch for the 'decarboxylation' steps; they occur at the isocitrate to alpha-ketoglutarate and alpha-ketoglutarate to succinyl-CoA transitions. Do not confuse the number of carbons in intermediates. Memorize the sequence: Citrate, Isocitrate, Alpha-ketoglutarate, Succinyl-CoA, Succinate, Fumarate, Malate, Oxaloacetate.
Clinical significance
Defects in TCA cycle enzymes like fumarase or succinate dehydrogenase lead to severe metabolic disorders and neurological impairment. Because the brain relies heavily on aerobic respiration, any failure in this cycle results in rapid ATP depletion and cellular death. This is why mitochondrial diseases are often multisystemic and devastating.
Introduction
The Tricarboxylic acid (TCA) cycle / Krebs cycle / Citric acid cycle is a series of 8 reactions in the mitochondrial matrix that oxidizes acetyl-CoA (2C) to CO₂, generating NADH, FADH₂, and GTP.
Core concept
One turn of TCA cycle (per acetyl-CoA): Acetyl-CoA (2C) + oxaloacetate (4C) → citrate (6C) → isocitrate → α-ketoglutarate (5C) + CO₂ → succinyl-CoA (4C) + CO₂ → succinate → fumarate → malate → oxaloacetate (regenerated). Products per turn: 3 NADH + 1 FADH₂ + 1 GTP + 2 CO₂. Per glucose (2 turns): 6 NADH + 2 FADH₂ + 2 GTP + 4 CO₂.
Go deeper
TCA cycle discovered by Hans Krebs (1937, Nobel 1953). Originally called 'citric acid cycle' for the first product (citrate, a tricarboxylic acid = 3 carboxyl groups). The cycle serves double duty: catabolism (energy extraction) and anabolism (intermediates drawn off for biosynthesis = amphibolic pathway).
From Class 10
After glycolysis, pyruvate is converted to acetyl-CoA, which enters the Krebs cycle — a central hub of cellular metabolism that extracts electrons for ATP production.