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Transport of Ammonia

&
Synthesis of Urea

Muhammad Saad Zaheer [ 138 (D) ]


Layout
1. Transport of Ammonia
 Sources of Ammonia
 Transport and destinations of Ammonia
 Disorders related to Ammonia Transport
2. Synthesis of Urea
 Site
 Urea Cycle
 Regulation of Urea Cycle
 Urea Cycle Diseases (UCDs)
Transport Of Ammonia
A. Sources of Ammonia
 Amino Acid
Transamination by ALT or AST
Forms NH3 *
Oxidative Deamination by Glutamate Dehydrogenase
Forms Aspartate*
* Form the Source of Nitrogen in Kreb Henseleit Urea Pathway
 Purine and Pyrimidine catabolism
 Intestinal and renal Glutamine Catabolism

 Bacterial Urease in the Intestines


B. Transport and Destination of Ammonia

Ammonia is transported in the form of:


• Alanine
[From Muscles to the Liver- “Glucose Alanine Cycle”]
• Glutamine
[From Muscle and Brain to Liver]
[From Liver to Kidneys]
• Urea
[From Liver to Kidneys]
[Little amount to Intestines as well]
C. Disorders
o Ammonia Produced by a variety of body Tissues.
o However its level is mainted at a low level of 5-50
micromoles per Litre.
o However when due to some disorder the amount of
Ammonia is raised in the blood, the situation may end up
in serious neurotoxicity of CNS.
o At Higher levels it may cause coma or Death
Types of Hyperammonemias
i. Acquired Hyperammonemia
• Commonly due to liver disease
• Cirrhosis of liver may result in decreased exposure of
blood to liver and consequently high levels of circulating
ammonia
ii. Hereditary Hyperammonemia
• Urea cycle enzyme disorder (usually recessive and
autosomal)
• Hyperammonemia during 1st few weeks of birth
• Treatment is dec. protein diet and AA binding compounds
which are then excreted from the body. e.g. phenly
butyrate given condenses with Glutamine to be excreted
as acetylglutamine.
Layout
1. Transport of Ammonia
 Sources of Ammonia
 Transport and destinations of Ammonia
 Disorders related to Ammonia Transport
2. Synthesis of Urea
 Site
 Urea Cycle
 Regulation of Urea Cycle
 Urea Cycle Diseases (UCDs)
Synthesis of Urea
A. Site
Occurs at Liver only
[Why? . . . Because Arginase is present only in
Liver]
B. Urea

From Aspartate From CO2 From Free NH3


C. Reactions
Kreb Hensleit Urea Pathway
2. Carbamoyl Phosphate formation
3. Citrulline Formation
4. Synthesis of Argininosuccinate
5. Cleavage of Argininosuccinate
6. Cleavage of Arginine into Ornithine and Urea
D. Regulation of Urea Synthesis
N-Acetylglutamate is essential activator of Carbamoyl
Phosphate Synthetase I, which is synthesized in a
reaction which is mediated by Arginine.
E. Disorders of Urea Cycle
• Hyperammonemias causing neurologic
disorders (discussed earlier).
• Treated by Hemodialysis and Reduction of
protein intake.
Thanks a lot !