Citric acid cycle: Pathway, energetics, and significance

• The Citric Acid Cycle, also known as the Krebs cycle or the Tricarboxylic Acid (TCA) cycle, is a cornerstone of cellular metabolism, pivotal in the breakdown and conversion of carbohydrates, fats, and proteins into usable energy.

• This cycle takes place in the mitochondrial matrix of eukaryotic cells, where it serves the dual purpose of generating high-energy molecules (ATP, NADH, and FADH2) and facilitating carbon dioxide excretion as a byproduct.

Citric Acid Cycle or Krebs cycle Pathway

Here's the colourful flowchart illustrating the Krebs Cycle Pathway:

Overview of the Krebs Cycle Steps

1. Formation of Citrate:

• Enzyme: Citrate synthase

• Process: Acetyl CoA (2 carbons) combines with oxaloacetate (4 carbons) to form citrate (6 carbons), releasing CoA.

2. Isomerization to Isocitrate:

• Enzyme: Aconitase

• Process: Citrate is rearranged into isocitrate via cis-aconitate as an intermediate.

3. Oxidation and Decarboxylation to α-Ketoglutarate:

• Enzyme: Isocitrate dehydrogenase

• Process: Isocitrate is oxidized to oxalosuccinate (6 carbons), then decarboxylated to α-ketoglutarate (5 carbons), producing NADH and releasing CO2.

4. Further Oxidation and Decarboxylation:

• Enzyme: α-Ketoglutarate dehydrogenase complex

• Process: α-Ketoglutarate is further oxidized and decarboxylated to form succinyl CoA (4 carbons), generating another NADH and releasing a second CO2 molecule.

5. Conversion to Succinate:

• Enzyme: Succinyl-CoA synthetase

• Process: Succinyl CoA is converted into succinate, producing one molecule of GTP (or ATP).

6. Oxidation of Succinate:

• Enzyme: Succinate dehydrogenase

• Process: Succinate is oxidized to fumarate, reducing FAD to FADH2.

7. Hydration to Malate:

• Enzyme: Fumarase

• Process: Fumarate is hydrated to form malate.

8. Oxidation to Oxaloacetate:

• Enzyme: Malate dehydrogenase

• Process: Malate is oxidized back to oxaloacetate, reducing NAD+ to NADH and preparing the cycle to begin anew.
  

Products of the Krebs Cycle per Acetyl CoA

1. 3 NADH molecules: For use in the electron transport chain.

2. 1 FADH2 molecule: Also for use in the electron transport chain.

3. 1 ATP (or GTP) molecule: Directly usable energy.

4. 2 CO2 molecules: Waste products released.

The Krebs cycle is integral to cellular energy production, feeding into the electron transport chain where NADH and

Energetics of the Citric Acid Cycle

• Each turn of the cycle, processing one Acetyl CoA molecule, yields:

• 3 NADH

• 1 FADH2

• 1 GTP (or ATP)

• The NADH and FADH2 produced enter the electron transport chain (ETC), where they contribute to the production of ATP through oxidative phosphorylation.

• NADH can generate approximately 2.5 ATP molecules, while FADH2 contributes around 1.5 ATP molecules per cycle.

Significance of the Citric Acid Cycle

• Energy Production: Major source of ATP, NADH, and FADH2, essential for cellular energy.

• Anaplerotic Reactions: Intermediates are precursors for biomolecules like amino acids and nucleotides.

• Metabolic Integration: Links the metabolism of carbohydrates, fats, and proteins via Acetyl CoA.

• Regulation: Enzymes in the cycle are tightly regulated based on the cell’s energy needs.

This simplified overview highlights the Citric Acid Cycle's critical role in energy production and metabolic regulation.