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The Citric Acid Cycle as a Hub, and Refilling It

The citric acid cycle oxidises acetyl groups and supplies intermediates for biosynthesis. Sustained withdrawals can deplete the intermediate pool if net replenishment does not match them. Anaplerotic reactions restore intermediates and help maintain cycle flux.

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What a learner can do afterwards

  • Names two intermediates withdrawn for biosynthesis and what they become.
  • Explains how sustained uncompensated intermediate loss can limit cycle flux, while adequate replenishment can maintain the pool.
  • Identifies a reaction that replenishes an intermediate and says when it is needed.

1 · Read

Pyruvate dehydrogenase converts pyruvate to acetyl CoA in mitochondria. Its acetyl group joins oxaloacetate to form citrate. Cycle reactions regenerate oxaloacetate, which can accept another acetyl group for another turn. Regeneration preserves the molecule's role, not every original carbon atom. Incoming acetyl carbons can remain in intermediates and leave as carbon dioxide on later turns.

Alpha-ketoglutarate can supply amino-acid synthesis, and oxaloacetate can supply gluconeogenesis or other biosynthesis. Withdrawal does not automatically stop the cycle. Sustained loss without matching net replenishment can shrink the intermediate pool. If oxaloacetate becomes limiting, less acetyl CoA can enter the cycle under otherwise unchanged conditions.

oxaloacetate + acetylcitratecycle reactionsoxaloacetate regenerated
Oxaloacetate is regenerated, but this is not a diagram tracing the identity of individual carbon atoms.

Per acetyl group, the cycle releases 2 CO2, forms 3 NADH and makes 1 ATP or GTP. Succinate oxidation reduces enzyme-bound FAD; its electrons pass onward without FAD leaving succinate dehydrogenase as a mobile carrier. NADH carries electrons to later reactions. This is net yield accounting, not a claim that the newest acetyl carbons leave in that turn.

Anaplerotic reactions provide net additions to the intermediate pool. Pyruvate carboxylase uses pyruvate, bicarbonate and ATP to make oxaloacetate. More acetyl CoA alone is not a net refill: its entry consumes oxaloacetate, which the ordinary cycle later regenerates. Supplying more acetyl groups does not replace sustained net intermediate losses.

Compare withdrawal with existing net replenishment. Additional refill needed is withdrawal minus replenishment when that difference is positive. Sustained excess loss can make the pool limiting; matched input maintains it. Heavy biosynthesis can increase refill demand, but growing cells are not always the maximum-demand case. Losing one refill enzyme need not cause depletion if another net input covers the loss.

loss exceeds net inputintermediate pool fallspool can limit flux
The risk comes from sustained uncompensated loss, not withdrawal alone.

The cycle regenerates intermediates while supplying biosynthesis. Net replenishment must match sustained losses if the intermediate pool is to remain available.

Lesson, questions and flashcards written for this dataset.

Readings and flashcards written for this dataset. Video resources by Khan Academy.

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The Citric Acid Cycle as a Hub, and Refilling It · Science, ages 20 to 21 · LightMySky