1. Amino acid metabolism

2. Content Introduction General Metabolism of amino acids Transamination
Deamination

3. Introduction
Amino acid catabolism is part of the whole body catabolism
Nitrogen enters the body in a variety of compounds present in the food, the most important being amino acids present in the dietary protein.
Nitrogen leaves the body as urea, ammonia, and other products derived from amino acid metabolism

4. Fate of amino acids Body protein Synthesis of tissue protein
Synthesis of Biological compounds
Synthesis of glucose, ketone bodies or fatty acids
Oxidation in TCA cycle to yield energy and CO2
Dietary protein
Synthesis of non essential amino acids
Amino acid Pool

5. General Metabolism of amino acids
Anabolic reactions where proteins are synthesized
Catabolic reactions where dietary proteins & body proteins are broken down to amino acids
Synthesis of specialized products such as heme, creatine, purines and pyrimidines

6. 4)Transamination: amino group is removed to produce carbon skeleton(keto acid),the amino group is excreted as urea
5) Carbon skeleton is used for the synthesis of non essential amino acids
6) Carbon skeleton is also used for gluconeogenesis or for complete oxidation
7) Amino acids are used for, other minor metabolic functions like conjugation,methylation, amidation etc..

7. Biosynthesis of urea Urea biosynthesis occurs in stages:
Transdeamination (Removal of α-amino group) by –a coupled process of transamination and deamination
Transamination forms Glutamate in peripheral cells
Deamination of glutamate forms ammonia in liver
(2) Minor pathway of oxidative and non oxidative deamination produce ammonia in peripheral cells
(3)Ammonia transport-Ammonia is transported to liver as glutamate, glutamine or alanine
(4) Detoxification of released ammonia – Ammonia is detoxified by specific reactions (Urea cycle) forming urea in liver

8. Transamination
Transamination interconverts pairs of α-amino acids and α -keto acids.
During Transamination, the amino group of an amino acid (amino acid R 1) is transferred to a keto acid (keto acid R 2), this produces a new keto acid while from the original keto acid, a new amino acid is formed

9. Aminoacid + Keto acid New Keto acid + New Amino acid

10. Role of B6 Phosphate (PLP) in transamination
The transfer of α-amino group from donor amino acid to Pyridoxal phosphate forms Pyridoxamine phosphate, and a keto acid.
The α-amino group is finally passed on to acceptor α-keto acid to form a new amino acid.

11. Eg: (1) ALT- Serum glutamate Alanine transferase
Reaction catalyzed can be represented as follows-

12. Eg: (2) AST-Serum glutamate-oxaloacetate-aminotransferase (SGOT)
Reaction catalyzed can be represented as follows-

13. Characteristics of Transamination
The general process of transamination is reversible ,occurs in all the tissues
It is catalyzed by Transaminases, also called amino transferases that require PLP(derived from Vit B6) as coenzyme
Specific transaminases exist for each pair of amino &keto acids.however only two make significant contribution for transamination ,aspartate transaminase (AST/SGOT) and alanine transaminase(ALT/SGPT)
Synthesis of non essential amino acids: all non essential aa can be synthesized by body from keto acids available from other sources. Eg: pyruvate to alanine, oxaloacetate to aspartate..
Glycine,alanine,serine,cysteine,asparagine,glutamine,aspartic acid,glutamic acid, asparagine,glutamine,tyrosine,proline- non essential amino acids

14. 5) Interconversion of aa ,so that equalization of quantity of non essential aa can be achieved 6) It diverts excess aa towards energy generation 7) The resultant α-Keto acid can be completely oxidized to provide energy, glucose, fats or ketone bodies depending upon the cellular requirement. 8) Amino acid undergo transamination to finally concentrate nitrogen in glutamate ,which is the only aa that undergoes oxidative deamination to a significant extent to liberate free NH3 for urea synthesis

15. 9) All aa except lysine,threonine, proline & hydroxyproline participate in transamination
10) Transamination is not restricted to α -amino groups.The δ -amino group of ornithine readily undergoes transamination.
11) Serum transaminases are important for diagnostic and prognostic purpose

16. Clinical significance of Transaminases
Serum aminotransferases such as serum glutamate-oxaloacetate-aminotransferase (SGOT) (also called Aspartate aminotransferase, AST) and serum glutamate-pyruvate aminotransferase (SGPT) (also called alanine transaminase, ALT) have been used as clinical markers of tissue damage, with increasing serum levels indicating an increased extent of damage. 

17. AST-Serum glutamate-oxaloacetate-aminotransferase (SGOT)
AST is found in the liver, cardiac muscle, skeletal muscle, kidneys, brain, pancreas, lungs, leukocytes, and erythrocytes
The enzyme is both cytoplasmic as well as mitochondrial in nature
Normal levels 8-20 U/L

18. AST… Elevated in Myocardial Infarction
Significantly elevated in liver disease, primary hepatoma
In alcoholic hepatitis: AST> ALT
↑ AST can also be seen in Muscle disorders like muscular dystrophies

19. ALT ALT is found primarily in the liver.
The normal serum activity ranges between Levels: U/L in males,10-30 U/L in females

20. ALT..
Very high levels in acute hepatitis of toxic /viral origin( U/L)
ALT elevation> AST elevation
Moderate increase in cirrhosis,hepatitis C ,NASH( U/L)

21. "Education is the best friend
"Education is the best friend. An educated person is respected everywhere. Education beats the beauty and the youth." Chanakya quotes  (Indian politician, strategist and writer, 350 BC-275BC)

22. Deamination
Removal of amino group from the amino acid as NH3 is termed as deamination

23. Histidase

24. Oxidative deamination
Libration of free ammonia from the amino group of amino acids coupled with oxidation.
Takes place mainly in liver & kidney
Purpose:
1) To provide ammonia for urea synthesis.
2) To provide alpha keto acid for energy
generation

25. This reaction is inhibited by ATP/GTP and stimulated by ADP/GDP thus when energy level is low more AA degraded to form alpha KG. In addition to equilibrating amino groups among available a-keto acids, transaminases funnel amino groups from excess dietary amino acids to those amino acids (e.g., glutamate) that can be deaminated
Only a few amino acids can be deaminated directly. Glutamate Dehydrogenase catalyzes a major reaction that effects net removal of N from the amino acid pool .  Glutamate Dehydrogenase is one of the few enzymes that can utilize either NAD+ or NADP+ as electron acceptor
(Enzyme)

26. The nitrogen atom that is transferred to α-ketoglutarate in the transamination reaction forming Glutamate,
is converted into free ammonium ion by oxidative deamination
Glutamate occupies a central place in the amino acid metabolism
Basically it acts as a collector of amino group of the amino acids.

27. This reaction is catalyzed by glutamate dehydrogenase(GDH)
This enzyme is unusual in being able to utilize either NAD+ or NADP+
Glutamate dehydrogenase is Zinc containing complex enzyme (six identical subunits), located in mitochondria, as are some of the other enzymes required for the production of urea.

28. Regulation of Glutamate dehydrogenase(GDH)
The activity of GDH is allosterically regulated
Guanosine triphosphate (GTP) and adenosine triphosphate (ATP) are allosteric inhibitors, whereas Guanosine diphosphate (GDP) and adenosine diphosphate (ADP) are allosteric activators
Hence, a lowering of the energy charge (more of ADP and GDP) accelerates the oxidation of amino acids favoring formation of alpha keto glutarate that can be channeled towards TCA cycle for complete oxidation to provide energy
Steroid & thyroid hormones inhibit GDH

29. Thus Transamination and deamination are coupled processes though they occur at distant places
Often termed as "transdeamination."

30. At right is summarized the role of transaminases in funneling amino N to glutamate, which is deaminated via Glutamate Dehydrogenase, producing NH4+.

31. Minor pathways of oxidative deamination
Via,
L-amino acid oxidase
2) D-amino acid oxidase

32. L-amino acid oxidase:
acts on all amino acids except hydroxy amino acids & dicarboxylic amino acids
Uses FMN as co-enzyme

33. + Release of
ammonia

34. D-amino acid oxidase:
Acts on glycine & D amino acid that may be formed by bacterial metabolism
Uses FAD as co-enzyme

35. Minor pathways of Non oxidative deamination
Some of the amino acids can be deaminated to liberate NH3 without undergoing oxidation
Types of reactions:
Dehydratases: requires PLP as coenzyme
Desulfhydrases: requires PLP as coenzyme
Histidase