Malate dehydrogenase

Definition

Malate dehydrogenase is an enzyme that catalyzes the reversible conversion of malate to oxaloacetate, utilizing NAD+ as a cofactor to produce NADH in the process. This reaction is crucial for cellular metabolism, as it plays a significant role in the citric acid cycle and also facilitates the transport of reducing equivalents into mitochondria through the malate-aspartate shuttle.

5 Must Know Facts For Your Next Test

1. Malate dehydrogenase is found in both mitochondrial and cytosolic forms, allowing it to function in different cellular locations.
2. The enzyme helps maintain the balance between malate and oxaloacetate, which is vital for proper functioning of the citric acid cycle.
3. In the malate-aspartate shuttle, malate dehydrogenase is critical for transferring reducing equivalents into mitochondria, particularly during high energy demand.
4. The reaction catalyzed by malate dehydrogenase is highly endergonic under standard conditions but can be driven forward by substrate-level regulation in cellular environments.
5. Deficiencies or dysfunctions in malate dehydrogenase can lead to metabolic disorders and impact overall cellular respiration efficiency.

Review Questions

• How does malate dehydrogenase contribute to the citric acid cycle and what would be the effect of its inhibition?
  • Malate dehydrogenase catalyzes the conversion of malate to oxaloacetate in the citric acid cycle, which is essential for regenerating oxaloacetate that combines with acetyl-CoA to form citrate. If this enzyme were inhibited, it would disrupt the flow of the cycle, leading to decreased production of NADH and ATP. This inhibition could ultimately reduce cellular energy availability and compromise various metabolic processes.
• Discuss how malate dehydrogenase is involved in the malate-aspartate shuttle and its significance for energy production.
  • Malate dehydrogenase plays a pivotal role in the malate-aspartate shuttle by facilitating the conversion of oxaloacetate to malate in the cytosol and vice versa in the mitochondria. This shuttle is important because it allows for the transfer of reducing equivalents from glycolysis into the mitochondria, where they can enter the electron transport chain for ATP generation. Without this enzyme's action, cells would be unable to efficiently use the reducing power generated during glycolysis.
• Evaluate the potential metabolic consequences of malate dehydrogenase deficiencies on cellular respiration and overall health.
  • Deficiencies in malate dehydrogenase can lead to impaired cellular respiration due to disrupted balance between malate and oxaloacetate. This impairment would reduce ATP production since fewer NADH molecules would be available for oxidative phosphorylation. Additionally, an inefficient energy metabolism could result in increased lactic acid production due to anaerobic pathways being favored, potentially leading to metabolic acidosis and affecting overall health by compromising energy-dependent cellular functions.

Related terms

Citric Acid Cycle: A series of enzymatic reactions that convert acetyl-CoA into carbon dioxide and generate energy in the form of ATP, NADH, and FADH2.

NADH:

A reduced coenzyme that carries electrons during cellular respiration, playing a key role in energy production within the mitochondria.

Malate-Aspartate Shuttle: A mechanism that transports electrons from the cytosol into the mitochondria, facilitating the transfer of reducing equivalents generated during glycolysis.