U01.01.091 Metabolic compartmentation

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Learning Objectives

  • Differentiate metabolic pathways based on their cellular location.
  • Identify pathways that require shuttling of intermediates between the mitochondria and cytosol.
  • Memorize the “dual-location” pathways essential for USMLE Step 1.

1. The Cellular Map

Efficient metabolism requires the physical separation of opposing pathways (e.g., fatty acid synthesis vs. oxidation) to prevent futile cycles.

Location Metabolic Pathways
Mitochondria * Fatty acid oxidation (β-oxidation)
* Acetyl-CoA production
* TCA cycle
* Oxidative phosphorylation
* Ketogenesis
Cytoplasm * Glycolysis
* HMP shunt
* Fatty acid synthesis
* Nucleotide synthesis
* Protein synthesis (RER/Ribosomes)
* Cholesterol synthesis (SER)
Both * Heme synthesis
* Urea cycle
* Gluconeogenesis

Activity

Clinical Correlate: The Malate-Aspartate Shuttle

Because NADH produced in the cytoplasm during glycolysis cannot cross the inner mitochondrial membrane directly, it uses shuttles (Malate-Aspartate or Glycerol-3-Phosphate) to deliver electrons to the Electron Transport Chain.

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