Ammonia is produced during amino acid metabolism and transported to the liver via glutamine and alanine. Glutamine acts as an ammonia storage molecule that is freely diffusible between tissues. High blood ammonia can cause neurological issues by disrupting the citric acid cycle. Hyperammonemia can be treated by trapping ammonia with drugs like sodium benzoate to remove it from the body.

2.  Ammonia is constantly liberated in the
metabolism of amino acids & other
nitrogenous compounds.
 At physiological pH, ammonia exists as NH4
+
ions.

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

5.  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.

6.  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.

7.  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.

8.  Glutamine is freely diffusible in tissues, hence
easily transported.
 Glutamine synthase (mitochondrial enzyme) is
responsible for synthesis of glutamine from
glutamate & ammonia, requires ATP & Mg2+.
 Glutamine can be deaminated by hydrolysis
to release ammonia by glutaminase.
 Glutaminase found in kidney & intestinal cells.

9. COO-
CH2
CH2
H – C - NH3
+
COO-
CO-NH2
CH2
CH2
H – C – NH3
+
COO-
NH4
+ H2OGlutamine
Synthetase
ATP ADP + Pi
Mg2+
Glutamate Glutamine
Glutaminase
H2O
NH4
+
LIVER
BRAIN
Deamination

10.  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.

11.  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.

13.  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.

14.  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.

15.  Increased levels of ammonia crosses BBB, 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+ NADP+
GDH
α- Ketoglutarate + NH3

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

17.  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.

18.  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.

19.  Textbook of Biochemistry-u Satyanarayana
 Textbook of Biochemistry-DM Vasudevan