Urea Cycle Overview

Introduction

• Biochemical pathway converting ammonia to urea.
• Ammonia is toxic and not water-soluble; urea is less toxic and water-soluble, allowing for excretion via urine.

Importance of Proteins

• Proteins: Major organic compounds in the body (10-12 kg in adults).
• Functions: Enzymes, hormones, clotting factors, receptors, etc.
• Proteins undergo proteolysis, breaking down into amino acids.
• Amino acids contain nitrogen; they produce nitrogenous waste.

Ammonia Production and Transport to the Liver

• Breakdown of proteins generates nitrogenous waste (toxic).
• Transport of nitrogenous waste to the liver is crucial.
• Ammonia cannot be released into blood directly (toxic).

Two Pre-Urea Cycle Steps

1. Transamination:

   • Transfer of amino group from one amino acid to another molecule (e.g., alpha-ketoglutarate to form glutamate).
   • Glutamate can circulate in the blood without releasing free ammonia.

2. Oxidative Deamination:

   • Glutamate undergoes oxidative deamination in the liver to liberate ammonia for urea synthesis.
   • Ammonia is transformed into urea through the urea cycle.

The Urea Cycle

• Also known as the Krebs-Henselit cycle (described in 1932).
• Involves 5 steps with distinct enzymes:
  • First two reactions happen in mitochondria:
    1. Formation of Carbamoyl Phosphate:
       • Ammonia + Carbon Dioxide ➔ Carbamoyl Phosphate.
       • Enzyme: Carbamoyl phosphate synthase 1 (CPS1).
       • Requires 2 ATP.
    2. Formation of Citrulline:
       • Carbamoyl Phosphate + Ornithine ➔ Citrulline.
       • Enzyme: Ornithine transcarbamylase (OTC).
       • One inorganic phosphate released.
  • Next three reactions occur in cytoplasm: 3. Formation of Argininosuccinate: - Citrulline + Aspartate ➔ Argininosuccinate. - Enzyme: Argininosuccinate synthetase (ATP-dependent). 4. Breakdown of Argininosuccinate: - Enzyme: Argininosuccinate lyase; splits into Arginine and Fumarate. 5. Formation of Urea and Ornithine: - Arginine + Water ➔ Urea + Ornithine. - Enzyme: Arginase.

Cycle Continuity

• Ornithine is recycled back to the mitochondria to combine with carbamoyl phosphate again.
• Urea enters the bloodstream and is excreted in urine.

Additional Resources

• Access lecture handouts and flashcards by joining the channel or Patreon community.
• Next video will feature mnemonics for the urea cycle's intermediate molecules and enzymes.

Conclusion

• Understanding the urea cycle is crucial for comprehending nitrogen metabolism and waste management in the body.