Urea________Cycle_______Presentation.pptx

The urea cycle is crucial for excreting excess nitrogen.
Nitrogen is essential for proteins, nucleic acids, and other biomolecules.
Breakdown of proteins produces toxic ammonia.
The urea cycle converts ammonia into urea, excreted by kidneys.

1. Urea Cycle: Functions, Steps, Products, and Regulation A Key Metabolic Pathway in Nitrogen Excretion By: Shivangi

2. Introduction The urea cycle is crucial for excreting excess nitrogen. Nitrogen is essential for proteins, nucleic acids, and other biomolecules. Breakdown of proteins produces toxic ammonia. The urea cycle converts ammonia into urea, excreted by kidneys.

3. Location of the Urea Cycle Occurs primarily in the liver. Involves both the mitochondrial matrix and cytoplasm of hepatocytes.

4. Urea Cycle Functions Detoxifies ammonia from amino acid catabolism. Converts ammonia into urea (less toxic). Maintains nitrogen balance. Prevents hyperammonemia.

5. Overview of the Urea Cycle Ammonia + Aspartate + 3 ATP + 2 CO2 → Urea + Fumarate + 2 ADP + AMP + 2 Pi + PPi + 2 H₂O 5 enzymatic steps: 2 in mitochondria, 3 in cytosol. Image source

6. Step 1 – Formation of Carbamoyl Phosphate Enzyme: Carbamoyl phosphate synthetase I (CPS I) Location: Mitochondria Inputs: Ammonia + CO 2 + 2 ATP Requires N- Acetylglutamate (NAG) as activator

7. Step 2 – Formation of Citrulline Enzyme: Ornithine transcarbamoylase Carbamoyl phosphate + Ornithine → Citrulline Citrulline is transported to the cytoplasm c arbamoyl phosphate enters the urea cycle and combines with ornithine to form citrulline in the presence of the enzyme ornithine transcarbamylase (OTC). The citrulline formed is then transported out of the  mitochondria   into the cytoplasm by ornithine translocase.

8. Step 3 – Formation of Argininosuccinate Enzyme: Argininosuccinate synthetase Citrulline + Aspartate + ATP → Argininosuccinate Location: Cytoplasm Citrulline and aspartate undergo a condensation reaction to form argininosuccinate in the presence of the enzyme argininosuccinate synthetase. Here, aspartate becomes the source of the second amine group on urea. This reaction utilises one ATP molecule.

9. Step 4 – Cleavage of Argininosuccinate Enzyme: Argininosuccinate lyase Argininosuccinate → Arginine + Fumarate Argininosuccinate is cleaved off to make arginine and fumarate in the presence of enzyme argininosuccinate lyase. The fumarate is used up in the production of NADH in the TCA cycle, and the arginine moves forward for the next step of the urea cycle.

10. Step 5 – Formation of Urea Enzyme: Arginase Arginine → Urea + Ornithine Ornithine re-enters mitochondria Arginine undergoes hydrolysis to yield urea and ornithine in the presence of arginase. Ornithine is transported back to the mitochondria, where it is used up in the second step of the cycle to form citrulline by combining with carbamoyl phosphate.

11. Summary of Enzymes Involved 1. CPS I 2. Ornithine transcarbamoylase 3. Argininosuccinate synthetase 4. Argininosuccinate lyase 5. Arginase

12. Products of the Urea Cycle Main Product: Urea Others: - Fumarate (enters citric acid cycle) - ADP, AMP - Pi, PPi - H₂O

13. Urea Cycle Regulation N- Acetylglutamate (NAG) activates CPS I Substrate concentrations: Ammonia, ornithine promote the cycle Integration with Citric Acid Cycle: Fumarate re-used

14. Integration with Citric Acid Cycle Fumarate → Malate → Oxaloacetate (used in gluconeogenesis) Shows metabolic interconnection

15. Urea Cycle Disorders (UCDs) Genetic enzyme deficiencies Lead to hyperammonemia Common enzyme defects: CPS I deficiency OTC deficiency Argininosuccinate synthetase deficiency (Citrullinemia) Argininosuccinate lyase deficiency (Argininosuccinic aciduria) Arginase deficiency ( Argininemia )

16. Symptoms and Diagnosis of UCDs Symptoms: - Vomiting, lethargy, seizures, developmental delay Diagnosis: - Blood ammonia, amino acid profile - Genetic testing

17. Treatment of UCDs Dietary protein restriction Ammonia scavenging drugs (e.g., sodium benzoate) Supplementation with arginine or citrulline Liver transplantation in severe cases

18. Conclusion The urea cycle is essential for ammonia detoxification Highly regulated process Disorders can be life-threatening but manageable with early diagnosis

19. References Fundamentals of Biochemistry by Voet and Voet

20. Thank You • Questions and Discussions