krebs cycle step by step

3 min read 15-03-2025

The Krebs cycle, also known as the citric acid cycle or tricarboxylic acid (TCA) cycle, is a crucial metabolic pathway in all aerobic organisms. It's the central hub of cellular respiration, bridging the breakdown of carbohydrates, fats, and proteins into usable energy in the form of ATP. Understanding its intricacies is key to grasping cellular energy production. This guide provides a detailed, step-by-step explanation of the Krebs cycle.

Preparing for the Cycle: Pyruvate's Journey

Before diving into the cycle itself, it's important to understand what fuels it. The process begins with pyruvate, a three-carbon molecule produced during glycolysis (the breakdown of glucose). However, pyruvate can't directly enter the Krebs cycle. It first undergoes a crucial preparatory step called pyruvate oxidation.

Pyruvate Oxidation: The Gateway to the Krebs Cycle

Decarboxylation: Pyruvate enters the mitochondrial matrix (the inner compartment of mitochondria). A carbon atom is removed as carbon dioxide (CO2), leaving a two-carbon molecule called an acetyl group.
Oxidation: The acetyl group is oxidized (loses electrons). These electrons are picked up by NAD+, reducing it to NADH.
Acetyl-CoA Formation: The acetyl group is then attached to coenzyme A (CoA), forming acetyl-CoA. This is the molecule that finally enters the Krebs cycle.

The Krebs Cycle: Eight Steps to Energy Production

Now, let's explore the eight enzymatic reactions of the Krebs cycle itself. Remember that this cycle happens twice for every glucose molecule because glycolysis produces two pyruvate molecules.

Step 1: Citrate Synthesis

Reactants: Acetyl-CoA (2C) and oxaloacetate (4C)
Enzyme: Citrate synthase
Product: Citrate (6C)
Description: Acetyl-CoA combines with oxaloacetate to form citrate, a six-carbon molecule. CoA is released.

Step 2: Citrate Isomerization

Reactants: Citrate
Enzyme: Aconitase
Product: Isocitrate
Description: Citrate is rearranged into isocitrate, a structural isomer. This involves dehydration followed by rehydration.

Step 3: Isocitrate Oxidation and Decarboxylation

Reactants: Isocitrate
Enzyme: Isocitrate dehydrogenase
Products: α-ketoglutarate (5C), NADH, CO2
Description: Isocitrate is oxidized, losing electrons to NAD+ (forming NADH), and a carbon dioxide molecule is released, resulting in α-ketoglutarate.

Step 4: α-Ketoglutarate Oxidation and Decarboxylation

Reactants: α-ketoglutarate
Enzyme: α-ketoglutarate dehydrogenase complex
Products: Succinyl-CoA (4C), NADH, CO2
Description: Similar to Step 3, α-ketoglutarate is oxidized, producing NADH and releasing CO2. The remaining four-carbon molecule is attached to CoA, forming succinyl-CoA.

Step 5: Substrate-Level Phosphorylation

Reactants: Succinyl-CoA
Enzyme: Succinyl-CoA synthetase
Products: Succinate (4C), GTP (or ATP)
Description: This step generates a small amount of ATP (or GTP, which is readily converted to ATP) through substrate-level phosphorylation. CoA is released.

Step 6: Oxidation of Succinate

Reactants: Succinate
Enzyme: Succinate dehydrogenase
Products: Fumarate (4C), FADH2
Description: Succinate is oxidized, and the electrons are transferred to FAD, forming FADH2. This is the only step of the Krebs cycle occurring in the inner mitochondrial membrane.

Step 7: Hydration of Fumarate

Reactants: Fumarate
Enzyme: Fumarase
Product: Malate (4C)
Description: Water is added to fumarate, converting it to malate.

Step 8: Oxidation of Malate

Reactants: Malate
Enzyme: Malate dehydrogenase
Products: Oxaloacetate (4C), NADH
Description: Malate is oxidized, generating NADH. Oxaloacetate is regenerated, completing the cycle and ready to accept another acetyl-CoA molecule.

The Krebs Cycle's Significance

The Krebs cycle is vital for cellular respiration. It yields:

High-energy electron carriers: NADH and FADH2, which carry electrons to the electron transport chain for ATP production.
ATP: A small amount directly through substrate-level phosphorylation.
Precursor molecules: Intermediates of the cycle serve as precursors for biosynthesis of amino acids, fatty acids, and other essential molecules.

Understanding the Krebs cycle, step by step, is essential for comprehending how our cells generate the energy needed for life's processes. Its intricate mechanisms highlight the elegance and efficiency of cellular metabolism.