Isocitrate dehydrogenase

Definition

Isocitrate dehydrogenase is an enzyme that plays a critical role in the citric acid cycle (Krebs cycle) by catalyzing the oxidative decarboxylation of isocitrate to alpha-ketoglutarate, producing NADH and releasing carbon dioxide. This reaction is essential for energy production and links carbohydrate metabolism to the Krebs cycle, showcasing its importance in cellular respiration and metabolism regulation.

5 Must Know Facts For Your Next Test

1. Isocitrate dehydrogenase exists in multiple forms, with mitochondrial NAD+-dependent and cytosolic NADP+-dependent variants, each playing different roles in metabolism.
2. The reaction catalyzed by isocitrate dehydrogenase is one of the major regulatory steps in the citric acid cycle, making it a key player in cellular energy metabolism.
3. This enzyme is sensitive to various factors such as substrate concentration, product inhibition by NADH, and allosteric regulation by ADP and ATP.
4. Deficiencies or mutations in isocitrate dehydrogenase have been linked to certain types of cancer, particularly gliomas and acute myeloid leukemia, where it can contribute to abnormal metabolic pathways.
5. The activity of isocitrate dehydrogenase is crucial for maintaining cellular redox balance by regulating levels of NADH and influencing pathways like the tricarboxylic acid cycle and gluconeogenesis.

Review Questions

• How does isocitrate dehydrogenase contribute to the regulation of the citric acid cycle?
  • Isocitrate dehydrogenase contributes significantly to the regulation of the citric acid cycle by catalyzing a critical step that transforms isocitrate into alpha-ketoglutarate. This reaction not only generates NADH, which is vital for energy production but also serves as a control point for the cycle. The enzyme's activity can be influenced by various factors including concentrations of substrates and products, making it a key regulator of cellular metabolism.
• Discuss the implications of isocitrate dehydrogenase mutations on cellular metabolism and their potential link to cancer.
  • Mutations in isocitrate dehydrogenase have significant implications for cellular metabolism, particularly in certain cancers like gliomas and acute myeloid leukemia. These mutations can lead to altered enzymatic activity, resulting in the accumulation of 2-hydroxyglutarate, an oncometabolite that disrupts normal cellular functions and promotes tumorigenesis. This highlights how changes in metabolic enzymes can shift cell metabolism towards cancerous pathways.
• Evaluate the role of isocitrate dehydrogenase in maintaining cellular energy balance and its impact on broader metabolic pathways.
  • Isocitrate dehydrogenase plays a pivotal role in maintaining cellular energy balance by regulating NADH production during the citric acid cycle. Its activity directly impacts energy availability within cells, influencing broader metabolic pathways like glycolysis and gluconeogenesis. When energy demands fluctuate, this enzyme adjusts its function based on substrate availability and cellular conditions, thereby ensuring metabolic flexibility and efficient energy utilization across various physiological states.

Related terms

Citric Acid Cycle: A series of chemical reactions used by all aerobic organisms to generate energy through the oxidation of acetyl-CoA, which ultimately produces ATP, NADH, and FADH2.

NADH:

A coenzyme that functions as an electron carrier in cellular respiration, playing a key role in the transfer of electrons to the electron transport chain for ATP production.

Alpha-Ketoglutarate: A key intermediate in the citric acid cycle that is formed from isocitrate through the action of isocitrate dehydrogenase, which can also serve as a precursor for amino acid synthesis.