Amino Acid Metabolism 1- 1st & 2nd Handouts

8/3/2019 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



Phosphate

C=O

NH3 +CO2 NH2


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H2O

Fumarate Arginine

Urea



Phosphate

C=O

NH3 +CO2 NH2

Excretion

Amino Acid Metabolism 1- 1st & 2nd Handouts

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