Why the TCA Cycle Is “Central”—Metabolic Rationale Why is the tricarboxylic acid (TCA) cycle considered the central pathway of cellular metabolism?

Difficulty: Easy

Correct Answer: Its intermediates are commonly used by other metabolic reactions (anaplerosis and cataplerosis)

Explanation:


Introduction / Context:
The TCA cycle sits at a crossroads where carbohydrates, fats, and proteins converge. It not only oxidizes acetyl units but also supplies intermediates for biosynthesis, making it a hub for both energy production and building-block generation.


Given Data / Assumptions:

  • Intermediates include citrate, α-ketoglutarate, succinyl-CoA, malate, oxaloacetate.
  • Anaplerosis replenishes TCA intermediates; cataplerosis removes them for biosynthesis.
  • Cells integrate multiple pathways simultaneously.


Concept / Approach:
Centrality refers to connectivity, not physical location. TCA intermediates feed amino acid synthesis (e.g., glutamate from α-ketoglutarate), heme synthesis (from succinyl-CoA), gluconeogenesis (via oxaloacetate/malate), and lipid synthesis (via citrate export for acetyl-CoA). This shared use underpins the description of the TCA as a central pathway.


Step-by-Step Solution:

List biosynthetic branches: amino acids, porphyrins, glucose (via OAA), fatty acids (via citrate).Explain replenishment: pyruvate carboxylase forms oxaloacetate; transamination interconversions balance pools.Conclude that widespread intermediate usage defines the TCA cycle’s centrality.


Verification / Alternative check:
Metabolic flux analyses show heavy traffic through TCA nodes and multiple entry/exit points during varied nutrient states.


Why Other Options Are Wrong:

  • Geometric “center” is irrelevant to metabolic centrality.
  • “All pathways depend solely upon it” is overstated; some microbes under certain conditions can bypass or modify TCA usage.
  • Other statements do not capture the integrative role of intermediates.


Common Pitfalls:
Equating “central” with “largest ATP producer”; oxidative phosphorylation, not TCA alone, yields most ATP.


Final Answer:
Its intermediates are commonly used by other metabolic reactions (anaplerosis and cataplerosis)

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