Which intermediate of the TCA cycle is regenerated at the end of each cycle and serves as the initial substrate for condensation with acetyl-CoA?

Explanation

## Oxaloacetate: The TCA Cycle Catalyst ### Role as Cycle Primer **Key Point:** Oxaloacetate is the 4-carbon acceptor molecule that is regenerated at the end of each TCA cycle turn. It is not consumed; rather, it catalyzes the entry and oxidation of acetyl-CoA. ### The Citrate Synthase Reaction **High-Yield:** The first committed step of the TCA cycle is: $$\text{Acetyl-CoA} + \text{Oxaloacetate} + \text{H}_2\text{O} \xrightarrow{\text{Citrate synthase}} \text{Citrate} + \text{CoA}$$ Oxaloacetate is regenerated at the end of the cycle when malate is oxidized by malate dehydrogenase. ### Why Oxaloacetate is Essential **Clinical Pearl:** Oxaloacetate concentration is critical for TCA cycle flux. In starvation or certain metabolic states, oxaloacetate depletion limits cycle function. This is why anaplerotic reactions (especially pyruvate carboxylase) are vital for replenishing oxaloacetate. ### Mnemonic **Mnemonic:** **O**xaloacetate = **O**pening molecule — it opens the cycle by accepting acetyl-CoA and is regenerated to repeat the process.