Citric Acid Cycle or Krebs Cycle Overview

Overview of the Citric Acid Cycle

The citric acid cycle, also known as the Krebs cycle or tricarboxylic acid (TCA) cycle, is a series of chemical reactions in the cell that breaks down food molecules into carbon dioxide, water, and energy. In plants and animals (eukaryotes), these reactions take place in the matrix of the mitochondria of the cell as part of cellular respiration. Many bacteria perform the citric acid cycle too, though they do not have mitochondria so the reactions take place in the cytoplasm of bacterial cells. In bacteria (prokaryotes), the plasma membrane of the cell is used to provide the proton gradient to produce ATP.

Sir Hans Adolf Krebs, a British biochemist, is credited with discovering the cycle. Sir Krebs outlined the steps of the cycle in 1937. For this reason, it is often called the Krebs cycle. It's also known as the citric acid cycle, for the molecule that is consumed and then regenerated. Another name for citric acid is tricarboxylic acid, so the set of reactions is sometimes called the tricarboxylic acid cycle or TCA cycle.

Citric Acid Cycle Chemical Reaction

The overall reaction for the citric acid cycle is:

Acetyl-CoA + 3 NAD⁺ + Q + GDP + P_i + 2 H₂O → CoA-SH + 3 NADH + 3 H⁺ + QH₂ + GTP + 2 CO₂

where Q is ubiquinone and P_i is inorganic phosphate

Steps of the Citric Acid Cycle

In order for food to enter the citric acid cycle, it must be broken into acetyl groups, (CH₃CO). At the start of the citric acid cycle, an acetyl group combines with a four-carbon molecule called oxaloacetate to make a six-carbon compound, citric acid. During the cycle, the citric acid molecule is rearranged and stripped of two of its carbon atoms. Carbon dioxide and 4 electrons are released. At the end of the cycle, a molecule of oxaloacetate remains, which can combine with another acetyl group to begin the cycle again.

Substrate → Products (Enzyme)

Oxaloacetate + Acetyl CoA + H₂O → Citrate + CoA-SH (citrate synthase)

Citrate → cis-Aconitate + H₂O (aconitase)

cis-Aconitate + H₂O → Isocitrate (aconitase)

Isocitrate + NAD+ Oxalosuccinate + NADH + H + (isocitrate dehydrogenase)

Oxalosuccinate α-Ketoglutarate + CO2 (isocitrate dehydrogenase)

α-Ketoglutarate + NAD⁺ + CoA-SH → Succinyl-CoA + NADH + H⁺ + CO₂ (α-ketoglutarate dehydrogenase)

Succinyl-CoA + GDP + P_i → Succinate + CoA-SH + GTP (succinyl-CoA synthetase)

Succinate + ubiquinone (Q) → Fumarate + ubiquinol (QH₂) (succinate dehydrogenase)

Fumarate + H₂O → L-Malate (fumarase)

L-Malate + NAD⁺ → Oxaloacetate + NADH + H⁺ (malate dehydrogenase)

Functions of the Krebs Cycle

The Krebs cycle is the key set of reactions for aerobic cellular respiration. Some of the important functions of the cycle include:

1. It is used to obtain chemical energy from proteins, fats, and carbohydrates. ATP is the energy molecule that is produced. The net ATP gain is 2 ATP per cycle (compared with 2 ATP for glycolysis, 28 ATP for oxidative phosphorylation, and 2 ATP for fermentation). In other words, the Krebs cycle connects fat, protein, and carbohydrate metabolism.
2. The cycle can be used to synthesize precursors for amino acids.
3. The reactions produce the molecule NADH, which is a reducing agent used in a variety of biochemical reactions.
4. The citric acid cycle reduces flavin adenine dinucleotide (FADH), another source of energy.

Origin of the Krebs Cycle

The citric acid cycle or Krebs cycle isn't the only set of chemical reactions cells could use to release chemical energy, however, it is the most efficient. It's possible the cycle has abiogenic origins, predating life. It's possible the cycle evolved more than one time. Part of the cycle comes from reactions that occur in anaerobic bacteria.