Amino Acid Metabolism 1- 1st & 2nd Handouts
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Transcript of Amino Acid Metabolism 1- 1st & 2nd Handouts
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Metabolism of Amino Acids
Disposal of Nitrogen
Faisal Khatib MD; PhD
Faculty of Medicine, University of
Jordan
Amino Acids: Disposal of Nitrogen
Amino Acids are NOT Stored in the Body Must be Supplied in the Diet
The body can synthesize nonessential A. Acids
Excess A. Acids are Rapidly Degraded Removal of Amino group:
Ammonia
The Carbon Skeleton of the Amino Acid ( keto Acid)
The Carbon Skeleton can be a Source of Energy orStored as Fat or Glycogen
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Nitrogen Metabolism
Entrance of Nitrogen to the body
Amino Acids
Other Compounds
Nitrogen Leaves the Body as
Urea
Ammonia
Uric Acid and other Compounds
Protein
Turnover
Replacement o
lost proteins
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Protein Turnover
Protein
ConcentrationSynthesis Degradation
Rate of Turnover: Variable
-Short Half Lives: Regulatory or Misfolded Proteins
(Minutes- Hours)
-Long Half Lives: Most Proteins (Days Weeks)
- Very Long Half Lives: Structural Proteins (Months Years)
Chemical Signals that Affect
Protein Degradation
Modified or Altered Proteins
N Terminal Residue
Ser Long Half Life
Asp: Short Half Life
Sequences Rich in Pro, Glu, Ser and Thr(PEST)
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Protein Degradation
Ubiquitin-Proteasome
Energy- Dependent
Endogenous Proteins
Lysosomes
Non-energy-
dependent
Extracellular and Cell
surface Proteins
Ubiquitin: Small Globular
Protein
------Gly CO NH Lys
Proteasome: Large Barrel-
Shaped
The Ubiquitin-Proteasome
Degradation Pathway
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Nitrogen Balance
Amino Acids are NOT Stored in the Body Protein turnover
Daily synthesis = Daily degradation
Excess A. Acids are Rapidly Degraded
Removal of amino group
The Carbon Skeleton can be used as
Source of Energy or
Stored as Fat or Glycogen Nitrogen Intake = Nitrogen excretion
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Removal of Amino
group by
Transamination
(Transaminase)
Substrate Specificity ofAminotransferases
Name according to
Aminogroup Donor
Glutamate Produced
Reversible reactions
In the Synthesis of
Nonessential Aminoacids
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Mechanism of
Action ofAminotransferases
Pyridoxal Phosphate (Vit B6)
Is required
Aldehyde
Amine
E N Z Y M E
S1 P1 S2 P2
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Plasma Level of
Aminotransferases
is used for Diagnosis
of
Cellular Damage
Oxidative Deamination of Glutamate
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Transport of Ammonia to Liver Ammonia is TOXIC Compound
Produced by Most Tissues
Converted to the nontoxic Urea in the Liver
Glu + NH3 Glutamine
Glu + Pyruvate Ketoglutarate + Alanine
ATP ADP + Pi
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Urea
The Major Disposal Form of Amino Groups
Derived from A.Acids
Ammonia
Aspartate
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O=
H2O
Fumarate Arginine
Urea
Agininosuccinate Ornithine
Aspartate Citrulline Carbamoyl
Phosphate
C=O
NH3 +CO2 NH2
3
2
1
4
5
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Formation of Carbamoyl Phosphsphate
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NH3 + CO2 +2ATP
Urea Synthesis: Net Reaction
NH3 + CO2 + ASP + 3ATP
Urea + Fumarate + 2ADP
+AMP +2Pi + PPi
+ 2ADP + Pi
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Urea Cycle is Regulated by N-Acetylglutamate
Activator of Carbamoyl
Phosphate Synthetase I
Its Concentration Increases after
A Protein-rich Meal
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Hyperammonimia
Plasma Level of Ammonia is Normally Low
High Levels >> Ammonia Intoxication:
Inherited Defects in the Urea Cycle Enzymes
Liver Diseases
Hepatitis, Toxins, Liver Cirrhosis
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Inherited Defects in the Urea Cycle
Enzymes Overall prevalence 1 in 30,000 birth
Most are Autosomal Recessive.
Can Lead to Serious Consequences:
Cerebral Edema, Mental Retardation
Coma, Death
Symptoms may Appear as Early as 2nd
Day after Birth.
H2O
Fumarate Arginine
Urea
Agininosuccinate Ornithine
Aspartate Citrulline Carbamoyl
Phosphate
C=O
NH3 +CO2 NH2
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H2O
Fumarate Arginine
Urea
Agininosuccinate Ornithine
Aspartate Citrulline Carbamoyl
Phosphate
C=O
NH3 +CO2 NH2
Excretion