Krebs Cycle TCA Cycle: Steps, Products and Importance

The Krebs cycle, also called the tricarboxylic acid (TCA) cycle or citric acid cycle, is a circular series of reactions in the mitochondrial matrix that completely oxidises the acetyl group of acetyl-CoA to carbon dioxide, harvesting high-energy electrons as NADH and FADH2. Discovered by Hans Krebs in 1937, it is the central hub of aerobic respiration for carbohydrates, fats, and amino acids alike.

It matters because most ATP from food ultimately comes from electrons captured here and cashed in by the electron transport chain. The cycle also supplies building blocks for amino acids and other molecules. Defects in its enzymes, though rare, cause severe energy failure, showing how indispensable this hub is.

Key Concepts

The cycle begins when acetyl-CoA (2C) joins oxaloacetate (4C) to form citrate (6C). Through two decarboxylations, citrate passes via isocitrate to alpha-ketoglutarate (5C), then to succinyl-CoA (4C), releasing 2 CO2 and producing 2 NADH. Succinyl-CoA → succinate yields one GTP by substrate-level phosphorylation. Succinate → fumarate produces FADH2; fumarate → malate → oxaloacetate produces a third NADH and regenerates the starting acceptor. Per acetyl-CoA: 3 NADH, 1 FADH2, 1 GTP, 2 CO2. Per glucose (2 acetyl-CoA): double these values.

How It Works

1. Acetyl-CoA + oxaloacetate → citrate (6C); CoA is released.
2. Citrate is rearranged to isocitrate, then oxidatively decarboxylated to alpha-ketoglutarate (5C): first CO2 and first NADH form.
3. Alpha-ketoglutarate → succinyl-CoA (4C): second CO2 and second NADH form.
4. Succinyl-CoA → succinate: one GTP (ATP equivalent) is made.
5. Succinate → fumarate makes FADH2; fumarate → malate; malate → oxaloacetate makes the third NADH, closing the loop.

Worked Example

Calculate the total yield from one glucose molecule passing fully through the Krebs cycle stage only. One glucose gives 2 pyruvate → 2 acetyl-CoA, so the cycle turns twice. Per turn: 3 NADH, 1 FADH2, 1 GTP, 2 CO2. For 2 turns: NADH = 2 × 3 = 6; FADH2 = 2 × 1 = 2; GTP = 2 × 1 = 2; CO2 = 2 × 2 = 4. Convert using modern P/O values (NADH = 2.5 ATP, FADH2 = 1.5 ATP): ATP value = 6 × 2.5 + 2 × 1.5 + 2 = 15 + 3 + 2 = 20 ATP equivalents from the Krebs stage per glucose. Add the link reaction's 2 NADH (5 ATP) separately when totalling whole respiration.

Common Misconceptions

• The Krebs cycle directly makes lots of ATP. Correction: It makes only 1 GTP per turn directly; its main harvest is NADH and FADH2 for the electron transport chain.
• Oxygen is used inside the cycle. Correction: No O2 participates directly; the cycle stops without oxygen only because NAD+ and FAD cannot be regenerated by the chain.
• One glucose equals one cycle turn. Correction: One glucose yields two acetyl-CoA, so the cycle turns twice per glucose.

Real-World Applications

Citric acid from this cycle's first compound is manufactured industrially using Aspergillus fungus for food and drinks. Doctors study cycle intermediates as biomarkers; elevated succinate signals certain tumours with defective succinate dehydrogenase. Nutrition and exercise science track cycle flux to understand endurance and metabolic flexibility. Agriculture researchers improve mitochondrial efficiency in crops for stress tolerance. The cycle's amphibolic intermediates also feed industrial production of amino acids like glutamate for flavour enhancers.

The Krebs cycle oxidises each acetyl-CoA to 2 CO2, harvesting 3 NADH, 1 FADH2, and 1 GTP per turn — 20 ATP equivalents per glucose. It is the mitochondrial hub where fuels converge and electrons are gathered for the final ATP payoff.