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Malate-aspartate shuttle

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Biological Chemistry II

Definition

The malate-aspartate shuttle is a biochemical system that facilitates the transfer of reducing equivalents, specifically electrons, from the cytosol into the mitochondria. This shuttle is vital because it allows NADH generated during glycolysis to be transported into the mitochondria, where it can contribute to ATP production through oxidative phosphorylation. This process is especially important in tissues with high energy demands, such as the heart and liver.

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5 Must Know Facts For Your Next Test

  1. The malate-aspartate shuttle operates primarily in liver, heart, and kidney cells, where high levels of aerobic metabolism occur.
  2. This shuttle uses two key enzymes: malate dehydrogenase and aspartate transaminase, to facilitate the conversion of oxaloacetate to malate and then back to aspartate.
  3. Malate can easily cross the mitochondrial membrane while maintaining the transfer of reducing equivalents without losing electrons.
  4. Unlike other shuttles like the glycerol phosphate shuttle, the malate-aspartate shuttle produces more ATP per molecule of NADH transferred.
  5. The shuttle mechanism also helps regenerate oxaloacetate in the cytosol, which is important for continued glycolysis.

Review Questions

  • How does the malate-aspartate shuttle function in terms of electron transport and ATP production?
    • The malate-aspartate shuttle transports electrons from NADH in the cytosol into the mitochondria by converting oxaloacetate into malate. This process allows malate to enter the mitochondria where it is converted back to oxaloacetate, transferring electrons to NAD+ and regenerating NADH. This mitochondrial NADH then enters the electron transport chain, ultimately leading to ATP production through oxidative phosphorylation.
  • Discuss the significance of the malate-aspartate shuttle in tissues with high energy demands compared to other shuttles.
    • The malate-aspartate shuttle is crucial for tissues like the liver and heart that require high levels of ATP for function. Unlike the glycerol phosphate shuttle, which only yields 1.5 ATP per NADH, the malate-aspartate shuttle generates 2.5 ATP per NADH due to its efficient transfer of electrons into the mitochondrial matrix. This makes it more effective in supporting aerobic metabolism and fulfilling energy needs in these high-demand tissues.
  • Evaluate how disruptions in the malate-aspartate shuttle could affect cellular metabolism and overall energy production.
    • Disruptions in the malate-aspartate shuttle can significantly impair cellular metabolism by preventing effective transport of reducing equivalents into mitochondria. If NADH cannot be efficiently transferred, oxidative phosphorylation may be hindered, leading to reduced ATP production. In high-energy tissues such as the heart and liver, this can cause metabolic dysregulation, reduced cellular function, and may even contribute to pathological conditions related to energy deficiency.

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