11. Ammonia Metabolism Biochemistry (1).pptx

Ammonia

1. Ammonia is constantly liberated in the metabolism of amino acids & other nitrogenous compounds. At physiological pH, ammonia exists as NH 4 + ions.

2. Amino acids – by transdeamination. Biogenic amines. Amino group of purines & Pyrimidine catabolism. By action of intestinal bacteria (urease) on urea.

3. There is a regular & constant production of NH3 from various tissues , its concentration in the circulation is low (10-20mg/dl). Body has an efficient mechanism for NH3 transport & its utilization for urea cycle.

4. The transport of ammonia between various tissues & the liver mostly occurs in the form of glutamate or alanine & not as free NH3. Alanine is important for NH3 transport from muscle to liver by glucose - alanine cycle.

5. Glutamine is a storehouse of NH3. It is present in highest concentration (8 mg/dl in adults) in blood among the amino acids. Glutamine serves as a storage & transport form of NH3. Synthesis mostly occurs in liver, brain & muscle.

6. Glutamine is freely diffusible in tissues, hence easily transported. Glutamine synthase (mitochondrial enzyme) is responsible for synthesis of glutamine from glutamate & ammonia, requires ATP & Mg 2+ . Glutamine can be deaminated by hydrolysis to release ammonia by glutaminase. Glutaminase found in kidney & intestinal cells.

7. COO - CH 2 CH 2 H – C - NH 3 + COO - CO- NH 2 CH 2 CH 2 NH 4 + H 2 O Glutamine S y nth e tase A TP Mg 2+ A D P + P i Glutamate H – C – NH 3 + COO - Glutamine G l utaminase H 2 O NH 4 + LIVE R BRAIN Deamination

8. Ammonia is essential for the synthesis of non-essential amino acids, purines, pyrimidines, amino sugars & aspargine. Ammonium ions are very important to maintain acid-base balance of the body.

9. Ammoniotelic: The aquatic animals dispose off NH3 into the surrounding water. Uricotelic: Ammonia is converted mostly to uric acid. E.g. Reptiles & Birds. Ureotelic: The mammals including man convert NH3 to urea. Urea is non-toxic, soluble & easily excreted.

10. Elevation of blood ammonia concentration is harmful to the Brain. Ammonia accumulation results in slurring of speech & blurring of the vision & cause tremors. It may lead to coma, finally death, if not corrected.

11. Increased levels of ammonia in blood. It may be genetic or acquired. Impairment in urea synthesis due to a defect in any one of the five enzymes in urea cycle. Acquired hyperammonemia may be due to hepatitis, alcoholism, where urea synthesis becomes defective, hence NH3 accumulates.

12. Increased levels of ammonia crosses blood brain barrier and formation of glutamate . More utilization of α -ketoglutarate. Decreased levels of α - Ketoglutarate in Brain. α -KG is a key intermediate in TCA cycle. Decreased levels impairs TCA cycle. Decreased ATP production. Glutamate NADPH + H + N A D P + GDH α - Ketoglutarate + NH3

13. Increased levels of ammonia results in Slurring of speech Blurring of the vision Convulsions Nausea, Vomiting Neurological Deficits Mental Retardation Coma & Death.

14. Increased levels of ammonia in blood & urine. Increased glutamine – in CSF, excreted in urine. Decreased blood urea levels. Urea cycle intermediates accumulate in blood & excreted in urine.

15. Intravenous administration of sodium benzoate, phenyllacetate. These condense with glycine & glutamate to form water soluble products that can be easily excreted. By this, ammonia can be trapped & removed from the body. In toxic hyperammonemia, hemodialysis may become necessary.

16. Describe formation, transport, storage, functions and toxicity of ammonia.