Isocitrate dehydrogenase

Definition

Isocitrate dehydrogenase is an important enzyme in the citric acid cycle that catalyzes the conversion of isocitrate to alpha-ketoglutarate while reducing NAD+ to NADH. This enzyme plays a critical role in energy production and cellular respiration, linking the cycles of glucose metabolism to the production of electron carriers for ATP synthesis.

5 Must Know Facts For Your Next Test

1. Isocitrate dehydrogenase exists in two forms: one that uses NAD+ as a cofactor and another that uses NADP+, which can lead to different metabolic pathways.
2. This enzyme is subject to regulation by various factors, including the availability of substrates, feedback inhibition from NADH, and activation by calcium ions.
3. Mutations in isocitrate dehydrogenase have been implicated in certain cancers, particularly gliomas, due to its role in metabolic reprogramming.
4. The reaction catalyzed by isocitrate dehydrogenase is irreversible, making it a key regulatory point in the citric acid cycle.
5. In mammals, there are three known isoforms of isocitrate dehydrogenase: IDH1 (cytosolic), IDH2 (mitochondrial), and IDH3 (mitochondrial), each having distinct functions and regulatory mechanisms.

Review Questions

• How does isocitrate dehydrogenase contribute to the overall energy production in the citric acid cycle?
  • Isocitrate dehydrogenase plays a pivotal role in the citric acid cycle by catalyzing the conversion of isocitrate to alpha-ketoglutarate while generating NADH. This reaction not only helps to continue the cycle but also produces a key electron carrier that feeds into the electron transport chain, ultimately contributing to ATP synthesis. The generation of NADH represents a crucial step in capturing energy from metabolic substrates.
• Discuss the regulatory mechanisms that control isocitrate dehydrogenase activity and their physiological implications.
  • Isocitrate dehydrogenase activity is regulated by various factors, including feedback inhibition by its product, NADH, which indicates sufficient energy levels in the cell. Additionally, calcium ions can stimulate its activity, linking its regulation to cellular energy demand and signaling pathways. This regulation ensures that the citric acid cycle operates efficiently according to cellular energy needs, maintaining metabolic homeostasis.
• Evaluate the potential consequences of mutations in isocitrate dehydrogenase on cellular metabolism and their link to cancer development.
  • Mutations in isocitrate dehydrogenase can lead to altered metabolic pathways, such as the accumulation of 2-hydroxyglutarate, which disrupts normal cellular processes and promotes tumorigenesis. These mutations are particularly significant in gliomas and other cancers, as they affect not only energy production but also epigenetic regulation and cell signaling. Understanding these mutations offers insights into cancer biology and potential therapeutic targets for treatment.

Related terms

Citric Acid Cycle: A series of enzymatic reactions that takes place in the mitochondria, converting acetyl-CoA into energy-rich compounds like NADH and FADH2 while producing CO2 as a waste product.

NAD+:

Nicotinamide adenine dinucleotide, a coenzyme that acts as an electron carrier in cellular respiration, accepting electrons during metabolic reactions.

Alpha-ketoglutarate: A key intermediate in the citric acid cycle that serves as a substrate for several metabolic pathways and is important for amino acid synthesis.