α-ketoglutarate dehydrogenase

Definition

α-ketoglutarate dehydrogenase is an important enzyme in the Krebs cycle that catalyzes the conversion of α-ketoglutarate to succinyl-CoA, while also producing NADH and releasing carbon dioxide. This enzyme plays a crucial role in cellular respiration, linking carbohydrate metabolism to energy production and regulating metabolic pathways.

5 Must Know Facts For Your Next Test

1. α-ketoglutarate dehydrogenase is a multi-subunit enzyme complex that requires cofactors like thiamine (vitamin B1), lipoic acid, and niacin (vitamin B3) for its activity.
2. The activity of this enzyme is regulated by the availability of its substrates and products, including α-ketoglutarate, succinyl-CoA, NAD+, and NADH.
3. Increased levels of NADH or succinyl-CoA can inhibit the enzyme's activity, demonstrating feedback inhibition in metabolic pathways.
4. This enzyme is crucial for the production of GTP or ATP, which are vital for cellular energy needs.
5. Dysfunction or mutations in α-ketoglutarate dehydrogenase can lead to metabolic disorders, as it can affect the overall efficiency of cellular respiration.

Review Questions

• How does α-ketoglutarate dehydrogenase contribute to the Krebs cycle and what are its main substrates?
  • α-ketoglutarate dehydrogenase plays a vital role in the Krebs cycle by catalyzing the conversion of α-ketoglutarate to succinyl-CoA, generating NADH in the process. Its main substrates are α-ketoglutarate and Coenzyme A, while its products include succinyl-CoA, NADH, and carbon dioxide. This reaction not only progresses the Krebs cycle but also integrates various metabolic pathways by linking carbohydrate metabolism to energy production.
• Discuss the regulatory mechanisms that control the activity of α-ketoglutarate dehydrogenase.
  • The activity of α-ketoglutarate dehydrogenase is primarily regulated through feedback inhibition. Increased concentrations of its products, such as NADH and succinyl-CoA, signal that enough energy has been produced, leading to a decrease in enzyme activity. Additionally, substrate availability also affects its function; low levels of α-ketoglutarate can slow down the reaction. These regulatory mechanisms help maintain metabolic balance within the cell.
• Evaluate the implications of α-ketoglutarate dehydrogenase malfunction on cellular respiration and overall metabolism.
  • Malfunctions in α-ketoglutarate dehydrogenase can have severe consequences for cellular respiration and overall metabolism. If this enzyme is defective or mutated, the conversion of α-ketoglutarate to succinyl-CoA is impaired, disrupting the Krebs cycle and leading to reduced production of ATP or GTP. This can result in a lack of energy for cellular functions and may cause metabolic disorders, highlighting the importance of this enzyme in maintaining efficient energy production within cells.

Related terms

Krebs Cycle: A series of chemical reactions used by all aerobic organisms to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins.

NADH:

A reduced coenzyme that acts as an electron carrier in the electron transport chain, playing a key role in cellular respiration by providing energy for ATP synthesis.

Succinyl-CoA: A key intermediate in the Krebs cycle that is formed from α-ketoglutarate and is used to generate GTP or ATP during cellular respiration.