2. Enter in the formation of A.A. pool
Fate of absorbed amino acids
Enter in the formation of A.A. pool

3. AA pool ~ 80 % in muscles ~ 10 % in liver
~ 5 % in kidney ~ 5 % in blood
Definition: AA POOL It include the free a.as distributed throughout the body
The a.a. pool contains 100 gm a.as.50% of these a.as are in the form of glutamate & glutamine (Why?)
In contrast to the amount of protein in the body (about 12 Kg in 70 Kg man), the a.a. pool is small (only 100 gm)
AA pool is not reserve !!
There is not a specific protein reserve in human body in contrast to saccharides (liver glycogen) and lipids (adip. tissue) !!

4. Overall metabolism of proteins
All proteins in the body are continuously degraded (metabolized) and newly synthesized
Free AA from food, tissue proteins and non-essential AA from synthesis , make AA pool
AA pool is used for:
i. New body proteins
ii. Specialized products (amines, NO, porphyrines, NA bases ...)
iii. Catabolic proceses (energy gain)

5. ►SOURCES & FATE OF THE AA. POOL:
Non essential a.a.s
synthesized in the body
Diatery proteins
Tissue proteins
a.a.s
Amino acid pool
Anabolism
Catabolism(Deamination)
Synthesis of
Fate of deamination products
Proteins
Other nitrogenous compounds
α- keto acid
Ammonia
►Aminosugars
►Nitrogenous bases
of phospholipids
►Purines & pyrimidines
►Neurotransmitters
►Niacin
►Creatine
►Heme
Krebs
cycle
►Tissue proteins
►Plasma proteins
►Enzymes
►Some hormones
►Milk
Ketone bodies
Synthetic
pathway
Catabolic
pathway
glucose
CO2+H2O
+ENERGY
Non essential
a.a.synthesis
Excreted
in urine
glutamine
Urea

8. GENERAL STRATEGY
·     Removal of N from amino acid by transamination (generally first or second step of amino acid catabolic pathways) and collection of N in glutamic acid
·   Deamination of glutamic acid with release of NH by glutamate dehydrogenase
Collection of N in glutamine or alanine for delivery to liver
·   Removal of NH4+ by :
i. secretion; or
ii. Conversion to urea or other less toxic form.

12. TRANSAMINATION Coenzyme: PLP (Pyridoxal phosphate)
► α-ketoglutarate & glutamate are often involved in transamination reactions
Coenzyme: PLP (Pyridoxal phosphate)

14. In transaminations, nitrogen of most AA is concentrated in glutamate
Glutamate then undergoes oxidative deamination and releases free ammonia NH3

15. GLUTAMATE TRANSAMINASE
DEAMINATION . ►
α- keto glutarate ◄
α- a.a. ◄ ►
NH3 ►
NAD(P)H+H
GLUTAMATE TRANSAMINASE
GLUTAMATE
DEHYDROGENASE
NAD(P) ► ►
H2O
α- keto acid
Glutamic acid ◄ ◄

16. Intracellular localization
Transamination  glutamate
cytosol
mitochondria
Glutamate Dehydregenase
glutamate
NH3
urea
synthesis
cytosol
Glu + NH3  Gln

17. Dehydrogenation deamination of glutamate is a reversible reaction
NAD(P)+
2-iminoglutarate
glutamate
main source of
ammonia in cells
2-oxoglutarate
GMD = glutamate dehydrogenase

18. Deamination products
α- keto acid
NH3

19. ►IMPORTANCE OF OXIDATIVE DEAMINATION
glutamate dehydrogenase enzyme is the only enzyme by which a.a. undergoes oxidative deamination in the mammalian tissue.
Oxidative deamination by glutamate dehydrogenase is an essential component of TRANSDEAMINATION.

21. ■Diagnostic value of transamination :
Transaminases are normally intracellular enzymes They are elevated in the blood when damage to the cells producing these enzymes occurs.
* Increase level of both ALT & AST indicates possible damage to the liver cells.
* Increase level of AST ALONE suggests damage to heart muscle , skeletal muscle or kidney.

22. Which cofactor is used by aminotransferases?Q.
Which cofactor is used by aminotransferases?

23. Pyridoxal phosphate

24. What are two main sources of ammonia in human body?Q.
What are two main sources of ammonia in human body?

25. Two main sources of ammonia in body
Dehydrogenation deamination of glutamate in cells of most tissues
Bacterial fermentation of proteins in large intestine ammonia diffuses freely into portal blood  portal blood has high concentration of NH3  NH3 is eliminated by liver (under normal cond.) ! !

26. Three ways of ammonia detoxication
Feature
Urea
Glutamine (Gln)
Glutamate (Glu)
Relevance
Compound type
Reaction
Enzyme
Energy needs
Intracell localiz.
Organ localiz.
     
H2CO3 diamide
urea cycle
5 enzymes
3 ATP
mitoch. + cytosol
only liver
   
γ-amide of Glu
Glu + NH3
Gln-synthase
1 ATP
cytosol
liver + other 
α-aminoacid
hydrog. amin. 2-OG
GMD
1 NADHa
mitochondria
mainly brain
a Equivalent of 3 ATP (compare respiratory chain).