1. UREA CYCLE
General Biochemistry

2. Introduction of Urea
• Discovered in 1727
• By Dutch scientist Herman Boerhaave
• In 1828, the German chemist Friedrich Wohler obtained urea
artificial
• By treating silver cyanate with ammonium chloride.
AgNCO + NH4Cl → (NH2)2CO + AgCl

3. Introduction of Urea (cont.…)
• This was the first time an organic compound was artificially
synthesized from inorganic starting materials, without the
involvement of living organisms.
• Wohler said
"I must tell you that I can make urea without the use of
kidneys, either man or dog. Ammonium cyanate is urea."

4. Introduction of Urea (cont.…)
• For this discovery, Wohler is considered by many the father of
organic chemistry.

5. Urea Cycle
•
•
•
•
Also known as “ornithine cycle”
cycle of biochemical reactions occurring in many animals
Produces urea ((NH2)2CO) from ammonia (NH3).
In mammals, the urea cycle takes place primarily in the liver,
and to a lesser extent in the kidney.

6. Urea Cycle (cont.…)
•
•
•
•
•
Urea is synthesized in the liver
Than secreted into blood stream
And taken up by the kidneys for excretion in the urine.
Partly takes place in mitochondria and partly in cytoplasm.
End product of protein metabolism.

7. Urea Cycle (cont.…)
• Ammonia is toxic to body
• Detoxified and converted into urea in urea cycle.
• The overall reaction of the urea cycle is as follow:
NH4+ + HCO3- + H2O + 3ATP + Aspartate Urea + 2ADP + AMP +
2Pi + PPi + Fumarate

8. Steps of Urea Synthesis
• Formation of carbamoyl phosphate:

9. Steps of Urea Synthesis (cont...)
• Formation of citrulline

10. Steps of Urea Synthesis (cont...)
• Formation of argininosuccinate

11. Steps of Urea Synthesis (cont...)
• Formation of arginine & fumarate

12. Steps of Urea Synthesis (cont...)
• Formation of urea & ornithine