The document summarizes amino acid metabolism and the metabolism of ammonia. It discusses: 1) Amino acids exist in an amino acid pool that increases after eating and decreases during fasting. Plasma amino acid levels range from 4-8 mg/dl. 2) Amino acids are used to synthesize proteins, peptides, and other biological molecules or undergo catabolism where the amino group is removed through transamination or deamination reactions. 3) Ammonia produced from amino acid catabolism is transported to the liver and converted to urea by the urea cycle. Elevated ammonia can be toxic and cause hyperammonemia.

1. Metabolism of
Amino Acids
By
N.Santhosh Kumar
Asst.Professor
Department of Biochemistry
SIMS & RH, Tumkur

2. The amount of free amino acids distributed
throughout the body is called amino acid pool.
It tends to increase in the fed state and tends to
decrease in the post absorptive state
Plasma amino acids ranges between 4 –8 mg/dl

3. Synthesis of non
essential amino
acids
Dietary protein
Breakdown of
tissue proteins
Amino acids
pool
Sources of amino acids Fate of amino acids
Formation of Structural
protein (eg: tissue proteins)
Biosynthesis of peptide
hormones, haemoglobin,
myoglobin & enzymes
Synthesis of biological
important peptides (eg:
Glutathione)
Biosynthesis of NPN
substances (eg: Urea, uric acid,
creatine, creatinine)

4. Nitrogen Balance

5. It evaluate the relationship between the Nitrogen -intake
(in the form of protein) & Nitrogen -excretion
Two situations are possible
Positive Nitrogen balance
Negative Nitrogen balance

6. Positive Nitrogen
Balance
Nitrogen intake > Nitrogen excretion
Occurs in growing infants and pregnant
woman

7. Negative Nitrogen
balance
Nitrogen intake <nitrogen excretion
occurs during serious illness, major injury &
trauma and also kwashiorkor and marasmus

8. Catabolism of
Amino Acids
(Removal of amino
group)

9. • All the catabolic pathway of amino acids (removal of amino
group) involves
Transamination,
Deamination reactions
to form α-keto acid and Ammonia.
• Further carbon skeleton either enters carbohydrate
(glucogenic) or lipid metabolisms (ketogenic)
• Ammonia is transported from the muscle to liver & converted
into urea than excreted.

10. Transamination
Reactions

11. .
Aminotransferase /
transaminase
Transfer of amino group from α-amino acid to α-”C”
atom of α-KG to form a new α-amino acid & a new α-
keto acid

12. Significance of transamination reactions
• This can provides the amino groups from many different a.a’s
into one common product L-glutamate
• L-GLU is the only amino acid whose α-amino group can be
directly removed at high rate by oxidative deamination.
• L-GLU can be used as an amino group donor in the synthesis
of non essential amino acids
• All amino acids can be transaminated except lysine,
threonine, proline and OH- proline.

13. Pyruvate
+
L-Glutamate
L- Alanine
+
α- Ketoglutarate
ALT / SGPT
PLP
Serum glutamate pyruvate transaminase (SGPT) /
Alanine amino transferase (ALT)
- Specific for liver diseases and also increases in acute
hepatitis, hepatic Jaundice

14. Oxaloacetate
+
L-Glutamate
L- Aspartate
+
α- Ketoglutarate
AST / SGOT
PLP
Serum glutamate oxaloacetate transaminase (SGOT)
Aspartate amino transferase (AST)
•Specific for the cardiac lesions & also acute liver
diseases, Hemolytic anemia.

15. Deamination
Reactions

16. • Removal of amino group from α-amino acid in the form
of ammonia with formation of α-keto acid.
• Occurs in liver and kidney.
• Deamination occurs in two ways:
A. Oxidative deamination.
B. Non oxidative deamination

17. Oxidative deamination
• Removal of ammonia from the amino acids with the link of
oxidation process
• It is catalyzed by enzymes Glutamate dehydrogenase and
L & D-amino acid oxidase.

18. Glutamate dehydrogenase(GLDH)
(In hepatocytes)
GTP , ATP & NADH
-
GLDH can use either NAD+ or NADP+ as the acceptor of
reducing equivalents
GLDH increased in cases of liver disease (hepatocellular
damage )
+
GDP , ADP

19. L & D-amino acid oxidases
(kidneys & liver)

20. Non-oxidative deamination
• Removal of ammonia from the amino acids without link of
oxidation process
• Dehydratase enzyme deaminates amino acids containing OH-
group & it needs PLP as coenzyme.
Serine + H2O Pyruvate + NH4
+
Serine dehydratase
Threonine dehydratase
Threonine α- ketoglutarate + NH4
+

21. METABOLISM
OF
AMMONIA

22. From amino acids via
Transamination &
deamination
Degradation of
biogenic amines
Ammonia
Formation and Metabolic fate of ammonia in the body
Converted to urea (urea cycle)
Synthesis of non essential
amino acids
Formation of Purines &
Pyrimidines
Maintains the acid base
balance via NH4
+ ions
From the amino
group of purines &
Pyrimidines
By the action of intestinal
bacteria (urease) on urea
Synthesis of Glutamine
Formation of amino sugars

23. Transport of Ammonia
• Ammonia is transported from muscle to liver in two transport
forms glutamine and alanine but not as free ammonia.
• I. Glutamine is a major transport & temporary storage form of
ammonia
Glutamate synthetase
Ammonia +Glutamate +ATP Glutamine +ADP+ Pi
Glutaminase
Glutamine + H2O Glutamate + NH4
+
Liver

24. Glutaminase
• Two isoenzymes of mitochondrial glutaminase
 Hepatic glutaminase - increases high protein intake
Renal glutaminase - increases in metabolic acidosis
• Excretion of ammonia into urine produced by the action of R-
glutaminase in renal tubular cells regulates acid base balance.
• Production of ammonia from intracellular renal glutamine
increase in metabolic acidosis And decreases in metabolic
alkalosis

25. • II. Alanine is important NH3
transporter from muscle to
liver by glucose – alanine
cycle (in starvation).
• Glutamate can transfer its α-
amino group to pyruvate by
the action of ALT to form
alanine.
• Liver promptly removes the
ammonia from the portal
blood.

26. Clinical Aspect
Of
Ammonia

27. • The concentration of ammonia in blood : 40 to 70 μgm/dl,
AMMONIA TOXICITY:
• Elevation of NH3 in blood is found to be toxic to the body.
Hyper ammonemia:
a) Acquired hyper ammonemia
• Usually the result of cirrhosis of the liver
• Leads to reducing the synthesis of urea.

28. b) Inherited hyper ammonemia :
results from genetic defects in the urea cycle enzymes.
Ammonia intoxication is characterized by:
– A peculiar flapping tremor.
– Slurring of speech.
– Blurring of vision.
– And in severe cases coma and death
due to increased NH3 concentration in blood & brain.

29. • High levels of ammonia leads to increased conc. of glutamine
– acts as an osmotically active solute in brain astrocytes,
• Triggers an uptake of water into the astrocytes to maintain
osmotic balance, leading to swelling of the cells – coma
• Terminal stages of ammonia intoxication characterized by
cerebral edema and increased cranial pressure

30. Treatment of hyper ammonemia
• Dietary Protein restriction
• Increased Arginine in diet, bypasses Arginosuccinase
defect
• Drugs like benzoate and phenyl acetate,
• Hemodialysis

31. Believe In Yourself And
All That You Are.
Know That There Is
Something Inside You
That Is Greater Than
Any Obstacle.

32. Next class
DISPOSAL OF AMMONIA
Ammonia has been disposed as Urea
by urea cycle
Thank you
Have a nice day to all