Pyruvate Oxidation

Conversion of Pyruvate to Acetyl Coenzyme A

• Location and Cellular Environment

  • The conversion process takes place within the mitochondrion, occurring across the mitochondrial membrane and inside the mitochondrial matrix.

• Carbon Balance and Stoichiometry

  • A glucose molecule consists of $6$ carbon atoms.

  • Glycolysis splits glucose into two pyruvate molecules, each containing $3$ carbon atoms.

  • During pyruvate oxidation, carbon dioxide ($\text{CO}_2$) is removed from each pyruvate molecule.

  • Due to the loss of $\text{CO}_2$, the resulting Acetyl Coenzyme A (Acetyl-CoA) consists of $2$ carbon atoms.

• Enzymatic Action and Cofactors

  • The reaction converting pyruvate to Acetyl Coenzyme A is catalyzed by the enzyme pyruvate dehydrogenase.

  • During this reaction, $2$ $\text{NAD}^+$ molecules are reduced to form $2$ $\text{NADH}$ molecules.

  • Coenzyme A attaches to the remaining $2$-carbon acetyl group.

• Chemical Bond Properties

  • The acetyl group is attached to Coenzyme A via a sulfur atom ($\text{S}$) linkage.

  • The sulfur bond ($\text{S}$) is unstable and can break easily, providing the thermodynamic drive to transfer the acetyl group into subsequent metabolic reactions.

The Citric Acid Cycle Intermediates and Sequence

• Formation of Citrate

  • Acetyl Coenzyme A, a $2$-carbon compound, reacts with Oxaloacetate, a $4$-carbon compound.

  • The combination of these two molecules yields Citrate (citric acid), which is a $6$-carbon compound.

• Sequential Intermediate Reactions

  • Citrate ($6$ carbons) is isomerized into Isocitrate ($6$ carbons).

  • Isocitrate undergoes oxidative decarboxylation, releasing a molecule of $\text{CO}_2$.

  • The removal of $\text{CO}_2$ converts the $6$-carbon compound into $\alpha$-ketoglutarate, which is a $5$-carbon compound.

  • $\alpha$-ketoglutarate ($5$ carbons) undergoes a second oxidative decarboxylation step, releasing another molecule of $\text{CO}_2$.

  • Loss of the second $\text{CO}_2$ transforms the molecule into Succinyl Coenzyme A, which is a $4$-carbon compound.

• Pathway Continuation and Oxaloacetate Regeneration

  • Succinyl Coenzyme A ($4$ carbons) progresses through the remaining reactions of the cycle to eventually regenerate Oxaloacetate ($4$ carbons).

  • The regenerated Oxaloacetate is available to combine with a new incoming molecule of Acetyl Coenzyme A, allowing the cycle to repeat continuously.