The proteins metabolism

Biochemistry for nurses: Unit 3
THE PROTEIN METABOLISM

• Protein Turnover = Continuous degradation and synthesis of proteins.
Replacement of 1-2% of the total body protein each day
• Amino acid pool = Accumulation of free AA in the liver and the blood: 75 % of
liberated AA from tissue proteins are reutilized
• Degradation (catabolism of AA) = Excess of AA are not stored! but rapidly
degraded for the synthesis of glucose (glycolosis) and lipids. Degradation of excess AA
causes an excess of nitrogen.
• Waste = Nitrogen excess is transformed into urea (80%) and ammonium (NH4
+) in
order to be thrown away in the urine.
(Liver and Blood)

NITROGEN BALANCE
• The amino acids are the main source of Nitrogen.
• Nitrogen balance (NB) is a comparaison between nitrogen
intake (Dietary proteins) and nitrogen loss (indigested
proteins in feces, waste excretion as urea (80%) and ammonia
(NH4
+) in the urine).
- For normal adult: Ingested nitrogen = excreted nitrogen
- Positive NB = Ingested nitrogen > excreted nitrogen
(children growth, pregnancy)
- Negative NB = Ingested nitrogen < excreted nitrogen
(may follow surgery, advanced cancer, marasmus)

Digestion and absorption of proteins
Digestion = degradation of the protein into AA by the digestive
system to make it absorbable by intestine.
Absorption = Transfert of the AA from the intestine to the blood

• Proteins are digested by proteases and peptidases.
• Protein digestion starts in the stomach.
• PEPSIN is an endoprotease which degrades food proteins in the stomach.

• TRYPSIN = Endopeptidase cleaves the peptide bond at the carboxyl
side of the Lysine and Arginine.
• CHYMOTRYPSIN = Endopeptidase cleaves the peptide bond at the
carboxyl side of the Tryptophan, Tyrosine and Phenylalanine.

Protein digestion is completed in the small intestine by brush border
enzymes carboxypeptidase, aminopeptidase, and dipeptidase.

Practise
ENDOPEPTIDASE:
• Trypsin = cleaves at the COOH side of Lysine and Arginine.
• Chymotrypsin = cleaves at the COOH side of Tryptophan, Tyrosine and
Phenylalanine.
• Tri or Dipeptidase = cleaves between AA of tri or dipeptides
EXOPEPTIDASE:
• Carboxypeptidase = removes AA from the COOH end
• Aminopeptidase = removes AA from the NH2 end
H2N-Val-Cys-Ala-Leu-Lys-Val-Glu-Arg-Gly-Phe-Phe-Tyr-Thr-Pro-Lys-Ala-COOH
Trypsin + Chymotrypsin
?
Tripeptidase + Aminopeptidase
+ Carboxypeptidase
Final products ?

Trypsin

ChymotrypsinTrypsin

ChymotrypsinTrypsin
H2N-Val-Cys-Ala-Leu-Lys-COOH
H2N-Val-Glu-Arg-COOH
H2N-Gly-Phe-COOH
H2N-Phe-COOH
H2N-Tyr-COOH
H2N-Thr-Pro-Lys-COOH
H2N-Ala-COOH

H2N-Gly-Phe-COOH
H2N-Phe-COOH
H2N-Tyr-COOH
H2N-Ala-COOH
Tripeptidase

H2N-Gly-Phe-COOH
H2N-Phe-COOH
H2N-Tyr-COOH
H2N-Ala-COOH
Tripeptidase
+ Aminopeptidase

H2N-Gly-Phe-COOH
H2N-Phe-COOH
H2N-Tyr-COOH
H2N-Ala-COOH
Tripeptidase
+ Aminopeptidase
+ Carboxypeptidase

H2N-Gly-Phe-COOH
H2N-Phe-COOH
H2N-Tyr-COOH
H2N-Ala-COOH
Tripeptidase
+ Aminopeptidase
+ Carboxypeptidase
H2N-Val-COOH
H2N-Cys-Ala-Leu-COOH
H2N-Lys-COOH
H2N-Val-COOH
H2N-Glu-COOH
H2N-Arg-COOH
H2N-Gly-Phe-COOH
H2N-Phe-COOH
H2N-Tyr-COOH
H2N-Thr-COOH
H2N-Pro-COOH
H2N-Lys-COOH
H2N-Ala-COOH

Summary:

• Protein Turnover = Continuous degradation and synthesis of proteins.
Replacement of 1-2% of the total body protein each day
• Amino acid pool = Dietary proteins and the catabolism of tissue proteins
provide free AA. 75 % of liberated AA from tissue proteins are reutilized.
• Degradation (catabolism of AA) = Excess of AA are not stored! but
rapidly degraded for the synthesis of glucose (glycolosis) and lipids.
Degradation of excess AA causes an excess of nitrogen.
• Waste = Nitrogen excess is transformed into urea (80%) and ammonium
(NH4
+) in order to be thrown away in the urine.
(Liver and Blood)

Definition of the Keto Acid
• The deamination of an Amino Acid (= removing of the amino group) forms
the corresponding Keto Acid.
• The Keto acid is also called « the carbon skeleton »

Definition of the Keto Acid
• The deamination of an Amino Acid (= removing of the amino group) forms
the corresponding Keto Acid.
• The Keto acid is also called « the carbon skeleton »
WASTE
REUSED!

BIOSYNTHESIS of UREA
Biosynthesis of urea is composed
by 4 stages:
1. Transamination
2. Oxidative deamination of
Glutamate
3. Ammonia transport
4. Reactions of the urea cycle.
80% of the excess amino acid
nitrogen forms Urea in order to
be thrown away in the urine.
Tissues
Liver

Transamination
•Transfert of the α-amino group (NH2) to the ketoglutarate to give GLUTAMATE
• The reaction is reversible.
• The reaction is catalysed by an enzyme (Aminotransferase) in presence of a
co-enzyme (PLP = Vit B6)
(TISSUES)

Oxidative deamination of Glutamate
• Formation of ammonia (NH3) from the amino group (NH2) of the Glutamate
by oxidative deamination.
• Glutamate is the only Amino Acid that undergoes oxidative deamination.
• Enzyme = Glutamate Dehydrogenase (GDH); Coenzyme = NAD+
(LIVER)

Amino acid oxidase reaction
• The amino acid oxidase (AAO) of liver
and kidney removes the nitrogen as
ammonium ion (NH4
+).
• Conversion of Amino Acids to an Imino
acids which are decomposed to a Keto
acid with release of NH4
+.
• Enzyme = AAO ; Coenzyme = Flavin
• The reduced Flavin is reoxidized by O2,
forming hydrogen peroxide (H2O2) which
then is split to O2 and H2O by
CATALASE.
(LIVER and KIDNEY)

Ammonia (NH3) Transport
• NH3 is very toxic to the nervous system!
• The NH3 produced by tissue are rapidly removed from circulation by the
Liver and converted to UREA
• Only traces (10-20 uG/dL) of NH3 are present in blood in normal
conditions
• Liver damage and metabolic disorders are associated with elevated
concentration of NH3 in the blood.
• In case of CIRRHOSIS (hepatic disease), NH3 rises to toxic levels,
consequently: Tremor, blurred, coma and ultimately death.
• The transport of NH3 from the tissue to the liver is done by
GLUTAMATE or GLUTAMINE as nontoxic forms.

Glutamine Synthase fixes NH3 as Glutamine.
• NH3 is fixed by GLUTAMATE to give
GLUTAMINE
• Enzyme = Glutamine Synthase (inside
tissue mitochondria)
• That reaction needs ENERGY to work!
(hydrolysis of ATP )
Tissues

UREA CYCLE
• UREA is the major end product of Nitrogen catabolism in human body.
• Synthesis of 1 molecule of UREA requires:
1. 3 molecules of ATP (Energy!)
2. 1 molecule of NH4+
3. 1 molecule of α- amino group (NH2) of Aspartate
• 5 enzymes catalyse the Urea Cycle in the liver cells:
1. Carbamoyl Phosphate Synthase I
2. Ornithine Transcarbamoylase
3. Argininosuccinic Acid Synthase
4. Argininosuccinase
5. Arginase

Summary of the Urea Cycle
2 NH3 + CO2 + 3 ATP
UREA + 2 ADP + Pi
+ AMP + Pi
Liver

Summary of the ammonia elimination
Amino acids
degradation
Amino group
Keto acids
« carbon skeletton »
Synthesis of glucoses
and lipids

Summary of the ammonia elimination
• 1 – 2 % of the body proteins are degraded and renewed daily
• Ammonia (NH3) is highly toxic.
• Ammonia (NH3) is converted to Urea
• Glutamine synthase converts NH3 to nontoxic glutamine
• Glutaminase releases NH3 for use in urea synthesis
• NH3, CO2 and the amide nitrogen of aspartate provide the
atoms of urea
• Hepatic urea synthesis takes place in part in the mitochondrial
matrix and in part in the cytosol.

Clinical correlation

Metabolic disorders of urea synthesis
• Extremely rare: Dysfunction of enzymes
• Disorders in urea synthesis

[NH3] in blood increases

NH3 intoxication
Intoxication is more severe
when the urea synthesis is
blocked at reactions 1 or 2

NH3 intoxication
Clinical symptoms:
•Vomiting
• Avoidance of high protein foods
• Irritability
• Lethargy
• Mental Retardation (Brain damage)

NH3 intoxication
Clinical Treatments:
• Low protein diet ingested
• Frequent small meals to avoid
sudden increase in blood of the
NH3 levels.
Clinical symptoms:
•Vomiting
• Irritability
• Lethargy

NH3 intoxication
Clinical Treatments:
• Low protein diet ingested
• Frequent small meals to avoid
sudden increase in blood of the
NH3 levels.
Clinical
improvement and
minimization of
Brain damage.
Clinical symptoms:
•Vomiting
• Irritability
• Lethargy

The proteins metabolism

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Viewers also liked

Viewers also liked (20)

Similar to The proteins metabolism

Similar to The proteins metabolism (20)

More from Dr Hakim Mehenni

More from Dr Hakim Mehenni (10)

Recently uploaded

Recently uploaded (20)

The proteins metabolism