Isocitrate

Definition

Isocitrate is a key intermediate in the citric acid cycle, also known as the Krebs cycle, which is a central metabolic pathway in cellular respiration. It is an important molecule involved in the oxidation of acetyl-CoA to produce energy in the form of ATP within the mitochondria of cells.

5 Must Know Facts For Your Next Test

1. Isocitrate is produced from citrate, the first intermediate in the citric acid cycle, through the action of the enzyme aconitase.
2. The oxidation of isocitrate to α-ketoglutarate, catalyzed by isocitrate dehydrogenase, is a rate-limiting step in the citric acid cycle and generates NADH, which is used in the electron transport chain to produce ATP.
3. Isocitrate dehydrogenase is an allosteric enzyme, meaning its activity can be regulated by the binding of other molecules, such as ADP and calcium ions, which can enhance its catalytic efficiency.
4. Mutations in the genes encoding isocitrate dehydrogenase have been linked to certain types of cancer, as the altered enzyme can lead to the production of an oncometabolite called 2-hydroxyglutarate, which can disrupt normal cellular processes.
5. The regulation of isocitrate dehydrogenase and the citric acid cycle as a whole is crucial for maintaining cellular energy homeostasis and coordinating various metabolic pathways within the cell.

Review Questions

• Explain the role of isocitrate in the citric acid cycle and its importance in cellular respiration.
  • Isocitrate is a key intermediate in the citric acid cycle, a central metabolic pathway in cellular respiration. It is produced from citrate by the enzyme aconitase and then undergoes oxidation, catalyzed by isocitrate dehydrogenase, to form α-ketoglutarate. This reaction is a rate-limiting step in the cycle and generates NADH, which is used in the electron transport chain to produce ATP, the primary energy currency of the cell. The regulation of isocitrate dehydrogenase and the overall citric acid cycle is crucial for maintaining cellular energy homeostasis and coordinating various metabolic pathways.
• Describe the allosteric regulation of isocitrate dehydrogenase and how it affects the activity of the citric acid cycle.
  • Isocitrate dehydrogenase, the enzyme that catalyzes the conversion of isocitrate to α-ketoglutarate, is an allosteric enzyme. This means its activity can be regulated by the binding of other molecules, such as ADP and calcium ions. The binding of these allosteric effectors can enhance the catalytic efficiency of isocitrate dehydrogenase, thereby increasing the rate of the citric acid cycle. This regulation allows the cell to adjust the activity of the cycle based on its energy needs and the availability of key cofactors, ensuring the efficient production of ATP through cellular respiration.
• Explain the link between mutations in isocitrate dehydrogenase and the development of certain types of cancer, and discuss the potential implications for cancer treatment.
  • Mutations in the genes encoding isocitrate dehydrogenase have been linked to the development of certain types of cancer. These mutations can lead to the production of an oncometabolite called 2-hydroxyglutarate, which can disrupt normal cellular processes and contribute to the uncontrolled growth and proliferation of cancer cells. The understanding of the role of isocitrate dehydrogenase in cancer has opened up new avenues for cancer treatment, as targeting the mutant enzyme or the downstream effects of the oncometabolite it produces could potentially be a therapeutic strategy. Ongoing research in this area aims to develop targeted therapies that can selectively inhibit the mutant isocitrate dehydrogenase and potentially improve outcomes for patients with these types of cancers.

Related terms

Citric Acid Cycle:

The citric acid cycle, or Krebs cycle, is a series of chemical reactions that occur in the mitochondria of cells to convert the acetyl group derived from carbohydrates, fats, and proteins into carbon dioxide and high-energy electrons that are used to produce ATP.

Acetyl-CoA:

Acetyl-CoA is a key molecule in cellular metabolism, serving as the entry point for the citric acid cycle. It is produced from the breakdown of carbohydrates, fats, and proteins and provides the acetyl group that is oxidized in the cycle to generate energy.

Dehydrogenase: Dehydrogenases are a class of enzymes that catalyze oxidation-reduction reactions, often involving the transfer of hydrogen atoms or electrons. Isocitrate dehydrogenase is a key enzyme in the citric acid cycle that catalyzes the conversion of isocitrate to α-ketoglutarate.