Biochemistry from Dr. Dhiraj J Trivedi SDM College of Medical Sciences and Hospital, Dharwad, India

1. FORMATION AND FATE
OF AMMONIA
Protein metabolism
Dr. Dhiraj J. Trivedi

2. From deamination of α- amino acids
 In liver amino acids under go deamination
either by oxidative or non oxidative
reaction to form α -Keto acids and free
ammonia is released
Amino acid Imino acid
Keto acid
Dehydrogenase Dehydrase
Desulphurase
Free NH3
1.
NADP+ NADPH

3. From deamination of Glutamic acid
 In liver and Kidney Glutamate under go
deamination by L- glutamate dehydrogenase
to form α -Keto glutarate and ammonia is
made free .
Glutamate Imino acid
α - Keto acid
L- glutamate Dehydrogenase
(GDH)
Free NH3
2.
NADP+ NADPH

4. From deamination of Glutamine
In Kidney Glutamine is deaminated by
glutaminase enzyme to form glutamate . Free
Ammonia release is excreted in Urine as
ammonium salt.
Glutamamine Glutamate
α - Keto acid
Glutaminase
Free NH3
3.
(GDH)
Free
NH3

5. From Intestinal bacterial flora
Considerable amount of ammonia is produce by protein
putrification by normal bacterial flora present in
small and large intestine. This is absorbed to the
blood via hepatoportal circulation.
Protein decayed protein
Bacterial putrification
Free NH3
4.
Blood via hepatoportal circulation

6. From Degradation of purine and
pyrimidine nitrogenous bases
 Small quantity of ammonia is produce by
deamination of adenylic acid , catabolism of
purine and oxidation of amines by amine
oxidase.
 This is very small fraction.
5.

7. Formation of Ammonia
AMMONIA
α- amino acids
Glutamic acid
Glutamine
Intestinal
bacterial
flora purine and
pyrimidine
nitrogenous bases
12
3
4
5

8. Amination of keto acids
 Ammonia released by deamination is
used for amination of α-Keto acids
 It result in the formation of non
essential amino acids .
Keto Glutarate Glutamate
Transaminase
NH3
1.
Fate of Ammonia

9. Amination of ketoglutarate to
glutamate
 Ammonia released by deamination is
used for amination of α-Keto acids
 It result in the formation of non
essential amino acids .
Keto Glutarate Glutamate
Glutamate DH
NH3
2.
Fate of Ammonia
H2O
NADH +H NAD+

10. Amination of glutamate to Glutamine
 One more molecule of Ammonia added
on to Glutamate to form Glutamine .
 Glutamate and glutamine are the major
buffering molecule for Ammonia.
GlutamineGlutamate
Glutamine synthetase
NH3
3.
Fate of Ammonia
Mg-ATP Mg-ADP + Pi

11. Detoxification of ammonia as
UREA
 Most of the ammonia produce in blood
is taken to the liver for the
conversion of UREA.
 In liver CO2 and NH3 forms
carbamoyl- phosphate which then
enter Urea cycle
4.
Fate of Ammonia

12. Fate of Ammonia
AMMONI
A
Amination of
keto acids
ketoglutarate
to glutamate
Glutamate
to
Glutamine Formation of
Urea
1
2
3
4

13. Explain the toxicity of ammonia
to brain cells. 5 MARKS

14. Toxicity of Ammonia
 Peripheral blood ammonia level is 30 –
60 microgram / dl
 Diffuses in to the cell and hence low
level in blood in normal health.
 Increase is highly toxic ,
 To brain , it may cause coma

15. Toxicity of Ammonia
Biochemical changes in brain
Enhances amination of α-Keto-glutarate to glutamate
Decreases TCA pool of α-Keto-glutarate
Slow down of TCA cycle
Cellular respiration and ATP formation affected
1.

16. Toxicity of Ammonia
Biochemical changes in brain
This reduces glutamic acid pool of brain cell
Result in decreased formation
of
inhibitory neurotransmitter
GABA
Increased ammonia enhances
glutamine formation
2.

17. Toxicity of Ammonia
Biochemical changes in brain
same transport protein
allows entry of tryptophane in brain cell
Result in increased formation of
Excitatory neurotransmitter
SEROTONIN
Increased brain glutamate increases
out flow of glutamine from brain cell
3.

18. Effect of ammonia toxicity
 Slurring of speech
 Blurring of vision
 Lethargy
 Vomiting
 Mental retardation
 Irrtative behavior
 Coma
 Death

19. Next class
Urea synthesis