The pathways of detoxification of ammonia

The normal level of ammonia in blood plasma is equal approximately 60mcM/L. Ammonia is a physiological irritant in small amount, but it is toxic product in a big quantity. Therefore there is need the detoxification of ammonia. Detoxification of ammonia occurs mainly in liver and kidneys. There are next pathways of detoxification of ammonia:

1) reductive amination

2) amides formation ammonium salts formation

3) ammonium salts formation

4) urea formation

5) purines and pyrimidines formation

Reductive amination is a pathway of detoxification of ammonia and biosynthesis of unessential amino acids:

Alfa-ketoglutaric acid+NH3àalfa-iminoglutaric acid+H2O

alfa-iminoglutaric acid+NADH2àglutamic acid+NAD

This process underlies the toxic effect of ammonia because ammonia binds alfa-ketoglutaric acid and affects CAC. It results in inhibition of CAC and increased amount of acetylCoA is used for ketogenesis. Hence ketoacidosis is developed.

The main pathway of detoxification of ammonia is amides formation. This process occurs in brain, kidneys and sceletal muscles. Only glutamic and aspartic acids undergo this process and glutamine (Gln) and asparagine (Asn) are formed respectively:

Glutamic acid(aspartic acid)+ATPàglutamine(asparagine)+AMP+PP

These reactions are catalyzed by glutamine synthase and asparagine synthase respectively. Gln and Asn are transport forms of ammonia.

The importance of amides formation:

1. temporary binding of ammonia and its transport

2. gln and asn are used in proteins biosynthesis

3. gln and asn are used in purines and pyrimidines formation

Gln and Asn are transported to liver and kidneys and there undergo the reverse reactions – cleavage of amides:

Glutamine(asparagine)àglutamic acid (aspartic acid)+NH3

These reactions are catalyzed by gln-ase and asn-ase respectively. Ammonia which is formed in liver is used on urea synthesis. Ammonia which is formed in kidneys is used on ammonium salts formation.

The formation of ammonium salts:

Ammonia and protons are excreted in the lumen of renal channels. Here the interaction of ammonia and protons occurs and ammonium is formed: NH3 + H⁺ à NH4⁺

Soluble salts of sodium, pottassium and calcium (chlorides, phosphates and sulfates) are excreted in the lumen of renal channels. These salts are dissociated to cations and anions. Anions bind with ammonium and salts of ammonium are formed, e.g.: NH4⁺ + Cl à NH4Cl

Thus, the importance of formation of salts of ammonium is in conservation of important ions in the body, such as sodium, pottassium and calcium and homeostatic role (neutrlization of acids).

The urea formation: this is one of the main processes of detoxification of ammonia in the body. It occurs mainly in liver:

NH3+CO2+H2O+2ATPà2ADP+H3PO4+carbomoylphosphate

Carbomoylphosphate+ornithineàcitrulline+H3PO4

Citrulline+aspartic acid+ATPàargininosuccinic acid+AMP+PP

argininosuccinic acidàarginine+ fumaric acid

arginine+H2Oàornithine+urea

Thus, nitrogen of urea formed due to the ammonia (50%) and asp (50%).

Final products of simple proteins metabolism

Final products of simple proteins metabolism are next:

1. urea

2. esteroglucuronic and esterosulfuric acids

3. ammonium salts

4. aldehydes which are formed in deamination of biogenic amines

5. hyppuric acid

6. CO2 and water

7. Creatinine