Download 1.Lect .AADegradation

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Fate of absorbed amino acids
Enter in the formation of A.A. pool
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) !!
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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)
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►SOURCES
& FATE OF THE AA. POOL:
Diatery proteins
Non essential a.a.s
synthesized in the body
Tissue proteins
a.a.s
Amino acid pool
Anabolism
Catabolism(Deamination)
Synthesis of
Fate of deamination products
Proteins
Other nitrogenous compounds
►Aminosugars
►Nitrogenous bases
►Tissue proteins of phospholipids
►Plasma proteins ►Purines & pyrimidines
►Neurotransmitters
►Enzymes
►Niacin
►Some hormones ►Creatine
►Milk
►Heme
α- keto acid
Ammonia
Krebs
cycle
glucose Ketone bodies CO2+H2O
+ENERGY
Non essential
a.a.synthesis
Synthetic
pathway
Urea
Catabolic
pathway
glutamine
Excreted
in urine
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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 NH4+
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.
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TRANSAMINATION
► α-ketoglutarate & glutamate are often
involved in transamination reactions
Coenzyme: PLP
(Pyridoxal
phosphate)
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In transaminations, nitrogen of most
AA is concentrated in glutamate
Glutamate then undergoes oxidative
deamination and releases free
ammonia NH3
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DEAMINATION
.
α- a.a. ◄
► α- keto glutarate ◄
GLUTAMATE
DEHYDROGENASE
GLUTAMATE TRANSAMINASE
α- keto acid ◄
►
Glutamic acid
◄
► NH3
►NAD(P)H+H
NAD(P)
► H2O
Intracellular localization
Transamination
 glutamate
cytosol
mitochondria
NH3
Glutamate
glutamate
Dehydregenase
urea
synthesis
cytosol
Glu + NH3  Gln
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Dehydrogenation deamination of glutamate
is a reversible reaction
GMD
HOOC CH CH2CH2COOH
NH2
HOOC C CH2CH2COOH
- 2H
NH
NAD(P)+
glutamát
glutamate
2-iminoglutarate
2-iminoglutarát
H2O
main source of
ammonia in cells
NH3 + HOOC C CH2CH2COOH
O
2-oxoglutarát
2-oxoglutarate
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GMD = glutamate dehydrogenase
Deamination products
NH3
α- keto acid
►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.
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■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.
Q.
Which cofactor is used by aminotransferases?
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Pyridoxal phosphate
R
CH
COOH
NH 2
H
C
HO
O
O
CH 2O P
OH
OH
H 3C
N
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Q.
What are two main sources of ammonia
in human body?
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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.)
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Three ways of ammonia detoxication
Feature
Urea
Glutamine (Gln)
Glutamate (Glu)
Relevance



Compound type
H2CO3 diamide
γ-amide of Glu
α-aminoacid
Reaction
urea cycle
Glu + NH3
hydrog. amin. 2-OG
Enzyme
5 enzymes
Gln-synthase
GMD
3 ATP
1 ATP
1 NADHa
mitoch. + cytosol
cytosol
mitochondria
only liver
liver + other
mainly brain
Energy needs
Intracell localiz.
Organ localiz.
a
Equivalent of 3 ATP (compare respiratory chain).
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