Isocitrate dehydrogenase

Definition

Isocitrate dehydrogenase is an enzyme that plays a crucial role in the citric acid cycle by catalyzing the oxidative decarboxylation of isocitrate to alpha-ketoglutarate. This reaction is important for the conversion of energy from carbohydrates and fats into usable forms through cellular respiration, and it helps maintain the flow of metabolites through the cycle.

5 Must Know Facts For Your Next Test

1. Isocitrate dehydrogenase has three main forms in mammals: IDH1 (cytosolic), IDH2 (mitochondrial), and IDH3 (mitochondrial), each playing different roles in metabolism.
2. The reaction catalyzed by isocitrate dehydrogenase releases carbon dioxide and reduces NAD+ to NADH, contributing to the electron transport chain for ATP production.
3. Isocitrate dehydrogenase is subject to regulation by various factors, including its substrates (isocitrate) and products (alpha-ketoglutarate), as well as allosteric regulators like ATP and ADP.
4. Mutations in the genes coding for isocitrate dehydrogenase can lead to metabolic diseases and are implicated in certain types of cancer, particularly gliomas.
5. The enzyme plays a key role in linking carbohydrate metabolism with fatty acid synthesis and amino acid metabolism, making it vital for cellular energy homeostasis.

Review Questions

• How does isocitrate dehydrogenase contribute to the overall efficiency of the citric acid cycle?
  • Isocitrate dehydrogenase contributes to the citric acid cycle by facilitating the conversion of isocitrate to alpha-ketoglutarate while generating NADH. This not only helps in harnessing energy from metabolic substrates but also ensures that there is a continuous flow of intermediates through the cycle. By producing NADH, it provides electrons for the electron transport chain, maximizing ATP production.
• What mechanisms regulate the activity of isocitrate dehydrogenase, and why are these mechanisms important for cellular respiration?
  • The activity of isocitrate dehydrogenase is regulated by allosteric interactions and feedback inhibition. Factors such as ATP and ADP levels influence its activity; high ATP levels inhibit it while high ADP levels promote its function. This regulation is essential because it allows cells to adapt their energy production based on demand, ensuring efficient use of resources during cellular respiration.
• Evaluate the implications of isocitrate dehydrogenase mutations in human health, particularly in relation to metabolic disorders and cancer.
  • Mutations in isocitrate dehydrogenase can have significant health implications, leading to metabolic disorders characterized by altered energy metabolism. In particular, these mutations are linked to certain cancers like gliomas, where they affect cellular respiration and lead to an accumulation of oncometabolites such as 2-hydroxyglutarate. This disruption can promote tumorigenesis by influencing cell proliferation and survival pathways, highlighting the enzyme's critical role beyond simple metabolic processes.

Related terms

Citric Acid Cycle: A series of biochemical reactions that occur in the mitochondria, generating energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins.

NAD+:

Nicotinamide adenine dinucleotide, a coenzyme involved in redox reactions, acting as an electron carrier and accepting electrons during the conversion of isocitrate to alpha-ketoglutarate.

Allosteric Regulation: The regulation of an enzyme's activity through the binding of molecules at sites other than the active site, which can enhance or inhibit enzyme function.