Download MBBS (Bachelor of Medicine, Bachelor of Surgery) 1st year (First Year) Biochemistry ppt lectures Topic 59 Formation And Transport Of Ammonia Notes. - biochemistry notes pdf, biochemistry mbbs 1st year notes pdf, biochemistry mbbs notes pdf, biochemistry lecture notes, paramedical biochemistry notes, medical biochemistry pdf, biochemistry lecture notes 2022 ppt, biochemistry pdf.
Formation and transport of Ammonia and its
associated disorders
Department of Biochemistry
Specific Learning Objectives
Outline formation and transport of ammonia
Describe importance of reactions catalyzed by glutamine synthetase,
glutaminase, and glutamate dehydrogenase
Role of Glutamine in Nitrogen metabolism
Ammonia Intoxication
List causes for hyperammonemia, its consequences, and treatments
to reduce blood ammonia levels
Sources of Ammonia
1. From glutamine
2. From bacterial action in intestine
3. From amines
4. From purines and pyrimidines
Role of Glutamine in Nitrogen Metabolism
1. When muscle degrades branched chain aa, it exports their nitrogen
as part of glutamine
2. In liver, hepatocytes use glutamine synthetase catalyzed reaction to
remove ammonia from blood
3. In brain, astrocytes use glutamine synthetase reaction to remove
neurotransmitter and recycle a precursor of it to neurons as part of a
glutamate/GABA cycle
Glutamine Transport Ammonia in Bloodstream
? Free ammonia produced in tissues is
combined with glutamate to yield glutamine
by glutamine synthetase and it requires ATP
? Glutamate and ATP react to form ADP and
-glutamyl phosphate intermediate which
reacts with ammonia to produce glutamine
and inorganic phosphate (Pi)
? Glutamine is a nontoxic transport form of
ammonia
?
Fig18.8: Lehninger Principles of Biochemistry by David L Nelson, 6th Ed
Cont--
Free ammonia converted to non toxic compounds before export from
extrahepatic tissues into blood and transport to liver or kidneys
For this transport function, glutamate critical to intracellular amino
group metabolism, is replaced by glutamine
Free ammonia produced in tissues combined with glutamate gives
glutamine by glutamine synthetase, this requires ATP
Glucose-Alanine Cycle: Alanine transport ammonia from skeletal muscle to liver
Two mechanisms are available in humans for transport
of ammonia from peripheral tissues to liver for its
ultimate conversion to urea
1) Combine ammonia with glutamate to form glutamine
(nontoxic transport form of ammonia) by glutamine
synthetase
? Glutamine is transported into blood and then to liver
where it is cleaved by glutaminase to produce
glutamate and free ammonia which is converted to
urea
Fig 19.13. Alanine serves as a carrier of ammonia and of the carbon skeleton of
pyruvate from skeletal muscle to liver. The ammonia is excreted and the pyruvate
is used to produce glucose, which is returned to the muscle.
Lippincott's Illustrated Reviews, Biochemistry, 6th Ed
2) Formation of alanine by transamination of pyruvate produced from
both aerobic glycolysis and metabolism of succinyl CoA generated by
catabolism of branched-chain aa
Alanine is transported by blood and then to liver, where it is converted
to pyruvate by transamination
Pyruvate is used to synthesize glucose by gluconeogenesis, which
can enter blood and be used by muscle
Ammonia Toxicity
Emptying cytosol of excess ammonia require reductive amination of
-ketoglutarate to glutamate by glutamate dehydrogenase and
conversion of glutamate to glutamine by glutamine synthetase
Both enzymes present at high levels in brain, although glutamine
synthetase reaction pathway imp for removal of ammonia
Cont--
High level of ammonium ions leads to increased level of glutamine,
which acts as osmotically active solute in brain astrocytes of CNS
provides nutrients, support to neurons
This triggers uptake of water into astrocytes to maintain osmotic balance
leads to swelling of cells and brain, which lead to coma
Cont--
Hyperammonemia: Blood ammonia level must be low because even slight
elevation leads hyperammonemia (toxic to CNS)
Normal blood ammonia is 30-60M
Elevated levels of ammonia in blood cause symptoms of ammonia
intoxication, which include tremor, slurring of speech, and blurring of vision
There are two types of conditions: Acquired and Hereditary
Cont--
Acquired: Cirrhosis of liver may result in formation of collateral
circulation around liver
As a result, portal blood is shunted directly into systemic circulation
and does not have access to liver
Therefore, conversion of ammonia to urea is severely impaired,
leading to elevated levels of ammonia.
Cont--
Hereditary: Genetic deficiency of each of five enzymes in urea cycle
pathway
X-linked ornithine transcarbamoylase/ornithine carbomyl transferase
deficiency is common of these disorders
In each case, failure to synthesize urea leads to hyperammonemia during
first weeks of birth
Treatment included restriction of dietary protein in presence of sufficient
calories to prevent catabolism
Two Clinical-cases discussed
15
Reference Books
1) Biochemistry, Lippincott's Il ustrated Reviews, 6th Ed
2) Harper's Il ustrated Biochemistry-30th Ed
3) Lehninger Principles of Biochemistry-6th Ed
Thank you
This post was last modified on 05 April 2022