Urea Cycle
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Urea Cycle

Protein Metabolism


Urea Cycle

Urea is the end product of protein metabolism.

Nitrogen (amino acids) → Ammonia (toxic) → Urea and excreted from the body.

Urea accounts for 80-90% of nitrogen containing substances excreted in the urine.

Urea is synthesized in liver and excreted through kidney.

Urea cycle was the FIRST METABOLIC CYCLE, and was given by Hans Krebs and Kurt Henseleit, hence also called as Krebs- Henseleit cycle.

The urea molecule has two amino groups, one from NH3 and the other from Aspartate.

Urea synthesis is 5- step cyclic process, with 5 distinct enzymes. First two enzymes are present in mitochondria and the rest in cytosol.



  1.  Synthesis of Carbamoyl Phosphate
    • Condensation Reaction
    • Enzyme - Carbamoyl phosphate synthase I, requires N-acetylglutamate for its activity
    • Takes place in mitochondria
    • NH4+ ions with CO2 to form carbamoyl phosphate
    • consumes 2 ATPs 
    • Irreversible and rate- limiting reaction
  2. Formation of Citrulline
    • Carbamoyl phosphate + Ornithine → Citrulline
    • Enzyme - Ornithine transcarbamoylase
    • Ornithine is regenerated and used in the urea cycle.
  3. Synthesis of Arginosuccinate
    • Condensation reaction
    • Citrulline with aspartate forms Arginosuccinate
    • Enzyme - Arginosuccinate synthase
    • second amino group of urea is used in this reaction
    • ATP molecule cleaved to AMP and Pi
  4. Cleavage of Arginosuccinate
    • Arginosuccinate cleaved to Arginine and Fumarate
    • Enzyme - Arginosuccinase
    • Arginine is the immediate precursor of urea.
  5. Formation of Urea
    • Arginine is cleaved to form Urea and Ornithine
    • Enzyme - Arginase
    • Ornithine, regenerated, enters mitochondria for its reuse in the urea cycle.



2 ATPs are utilized for synthesis of Carbomyl phosphate

1 ATP is converted to AMP and PPi, to produce arginosuccinate, which equals 2 ATPs.

Hence, total 4 ATPs are utilized in the reaction.

This cycle is totally irreversible.

Mnemonic for molecules involved : Orange Colored Cats Always Ask For Awesome Umbrellas.

Orange - Ornithine

Colored - Carbamoyl phosphate

Cats - Citrulline

Always - Aspartate (enters the cycle)

Ask - Arginosuccinate

For - Fumarate (leaves the cucle )

Awesome - Arginine

Umbrellas - Urea

Mnemonic for Enzymes involved : Can Our Aunts Aim Accurately

Can - Carbamoyl synthase I

Our - Ornithine transcarbamoylase

Aunts - Arginosuccinate synthase

Aim - Arginosuccinase

Accurately - Arginase


Video Illustration: https://youtu.be/K3rVr_SfXo8


Essentials of Biochemistry, 2nd Edition, Satyanarayana

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