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 AmmoniaA. 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 Alanine

[From Muscles to the Liver- “Glucose Alanine Cycle”]• GlutamineGlutamine

[From Muscle and Brain to Liver]

[From Liver to Kidneys]• UreaUrea

[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. SiteOccurs 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

1. Carbamoyl Phosphate formation

2. Citrulline Formation

3. Synthesis of Argininosuccinate

4. Cleavage of Argininosuccinate

5. 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 !