🧬 The Urea Cycle – Nitrogen Removal & Key Enzymes

The urea cycle is a biochemistry favorite on the DAT. It’s the body’s main way to safely eliminate toxic nitrogen—a byproduct of amino acid metabolism. This pathway involves both mitochondrial and cytosolic steps, and it connects to several areas of clinical importance (like hyperammonemia).

Today’s breakdown includes:

  • Urea cycle purpose & overview

  • Step-by-step enzymes

  • ATP cost and transport

  • DAT-style questions

🔬 What Is the Urea Cycle?

The urea cycle, also called the ornithine cycle, converts ammonia (NH₃) into urea, which is excreted via the urine. It prevents ammonia buildup, which is toxic to the brain.

🧠 Key inputs: NH₃ + CO₂ → Urea

🔁 Steps and Enzymes of the Urea Cycle

Step Enzyme Key Product Location
1 Carbamoyl phosphate synthetase I (CPS I) Carbamoyl phosphate Mitochondria
2 Ornithine transcarbamylase (OTC) Citrulline Mitochondria
3 Argininosuccinate synthetase Argininosuccinate Cytosol
4 Argininosuccinate lyase Arginine + Fumarate Cytosol
5 Arginase Urea + Ornithine Cytosol

🧠 Mnemonic: "Ordinarily, Careless Crappers Are Also Frivolous About Urination"

⚙️ Energy and Transport Notes

  • The cycle uses 3 ATP equivalents

  • Citrulline moves from mitochondria → cytosol

  • Ornithine is regenerated and cycles back in

🩺 DAT Clinical Tie-In: Hyperammonemia

Type Cause
Type I CPS I deficiency
Type II Ornithine transcarbamylase deficiency (OTC)
Acquired Liver dysfunction (e.g., cirrhosis)

Symptoms: Vomiting, confusion, lethargy, coma (due to ammonia buildup)

✅ Know enzyme names and where disruption causes backup of substrates.

📈 DAT-Style Practice Question

Q: A patient has elevated blood ammonia and citrulline. Which enzyme is likely deficient?
A: Argininosuccinate synthetase

🎯 DAT Strategy Tips

✅ Memorize the enzyme sequence (CPS I → OTC → ASS → ASL → Arginase)
✅ Know which steps happen in mitochondria vs cytosol
✅ Understand ATP cost and ammonia detox
✅ Review clinical correlations (especially OTC deficiency)

See more biochem visuals at kingofthecurve.org/studyscience

🚀 Call-to-Action

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🧠 Subarachnoid Hemorrhage (SAH): The Thunderclap Headache You Can’t Miss on the USMLE