Protein Metabolism

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Protein MetabolismUrea Cycle

• By
• Dr. Samer Zahran

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Learning Objectives

• Describe the three mechanisms used by humans for
  removal of the nitrogen from amino acids prior to
  the metabolism of their carbon skeletons.
• Outline the sequence of reactions in the urea
  cycle and trace the flow of nitrogen from amino
  acids into and out of the cycle.
• Define the terms and give examples of glucogenic
  and ketogenic amino acids

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Learning Objectives ( cont. )

• Summarize the sources and use of ammonia in
  animals and explain the concept of nitrogen
  balance.
• Explain the biochemical basis and the therapeutic
  rationale for treatment of phenylketonuria and
  maple syrup urine disease.

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• Proteins or polypeptides are polymers of
• amino acids.
• They perform many essential functions in
• mammalian body.
• These functions are
• I - Dynamic functions
• II- Structural functions

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• I - Dynamic functions
• a) Transport functions
• Albumin that transports some drugs, calcium, bile
  pigments and FFA
• Hemoglobin that transports oxygen.
• Transferrin that transports iron.
• Lipoproteins that transport lipid.

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• b) Metabolic control as they enters in the
  formation of enzymes and some hormones, e.g.
  Insulin and glucagon.
• c) Contraction , e.g. Proteins of muscles
• (actin and myosin)
• d) Protection, e.g. Immunoglobulins.
• e)Blood clot e.g.Fibrinogen,thromboplastin, and
  prothrombin.

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• II- Structural functions
• a) Essential component of cell membrane
• cytoplasm, cell organells and receptors.
• b) Enter in the structure of collagen,
• elastin, keratin, and rhodopsin

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• Sources of Dietary Proteins
• 1- Animal as milk, fish, meat and eggs.
• 2- Plant as cereals and beans.

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• Fate of absorbed amino acids
• Anabolic pathway
• Catabolic pathway

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• Anabolic pathway
• Amino acids enter in the formation of
  proteins for wear and tear, plasma proteins,
  hemoglobin, enzymes, some hormones
• also enter in the formation of non protein
  nitrogenous compounds (NPN) as purines,
  pyrimidines, creatine and thyroxine.

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• Catabolic pathway
• a) Urea formed in the liver, is considered
  as
• the main metabolic endoproduct of protein
• catabolism.
• b) Supplying energy 1 gram protein yields
• 4.1 K cal, only if there is shortage in
• carbohydrate and fats.

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Nitrogen Balance There is no storage (depot)
for protein, but there is a certain percentage of
protein that undergoes a constant process of
breakdown and resynthesis i.e. turnover. This is
a normal process an essential feature of what is
called "nitrogen balance". Nitrogen balance
is a comparison between the intake of nitrogen
(mainly in the form of dietary protein) and the
excretion of nitrogen (mainly in the form of
undigested protein in stool and urea and ammonia
in urine). Also nitrogen output is through nails,
hair and desquamated skin.
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Nitrogen equilibrium The normal adult
human will be in nitrogen equilibrium when N2
lost (in urine, feces and sweat) just balanced by
N2 in diet intake. N2 LOST
N2 INTAKE
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• Positive nitrogen balance
• A condition in which there is increase in
  the N2 intake over the output.
• N2 LOST lt N2
  INTAKE
• It may occur in growth, pregnancy or
  convalescence from diseases.

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• Negative nitrogen balance
• A condition in which there is either
  decreased
• N2 intake as in
• starvation, poverty,
• malnutrition,maldigestion, malabsorption,
• severe vomiting, severe diarrhea
• Or increased N2 output as in
• hemorrhage, burns,
• old age or debilitating disease.
• N2 LOST gt N2
  INTAKE

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N.B. 1- Daily protein needs are One
gram protein per kilogram body weight (i.e. about
70-100 gm protein per day). At least part of
this protein should be of high biological
value. A protein of high biological value
should contain all essential amino acids.
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• 2- essential amino acids are amino acids that are
  not synthesized in our body and hence, must be
  supplied in food.
• They are arginine, histidine, valine, leucine,
  isoleucine, lysine, methionine, threonine,
  phenylalanine and tryptophan.
• If nine of the ten essential amino acids are
  present in certain type of food, this food is
  considered to contain protein of low biological
  value.

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• General Metabolism of Proteins
• Complete breakdown of proteins and amino
  acids give rise to
• Urea Co2 H2O Energy.

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• The major pathway for amino acids excess after
  protein synthesis is the removal of the amino
  group and its conversion to ammonia (as there is
  no amino acid storage).
• The liver is the major site of removal of amino
  group from amino acids..

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• The amino group is removed by different
  mechanisms
• 1. Transamination
• 2. Oxidative deamination
• 3. Non-oxidative deamination
• 4. Transdeamination

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• I . Transamination
• It transfers the amino group from an amino acid
  to a -keto acid.
• All the amino acids participate in the reaction
  of transamination except threonine and lysine.
• Vitamin B6 is required as a coenzyme.
• Its enzymes are termed transaminases

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a) Aspartate transaminase (AST) or(GOT)
Glutamic acid Oxaloacetic acid
a-Ketoglutaric acid Aspartic acid
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b) Alanine transaminase (ALT)or(GPT)
Glutamic acid Pyruvic acid
a-Ketoglutaric acid Alanine
Transaminases are cytosolic and mitochondrial
enzymes. It is a freely reversible process.
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Biological importance of Transamination

• 1- Synthesis of new non-essential amino acids.
• 2- Degradation of most amino acids except lysine
  and threonine.
• 3- Formation of components of citric acid cycle
  (filling up reaction of citric acid cycle).
• 4-Transaminase enzymes are used in diagnosis and
  prognosis of the diseases.

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• N.B. Transaminase enzymes are present inside the
  cells and small traces are present in the blood
  (5-40 IU/L).
• The increase in their level denote cell damage
  with the release of enzymes from the destructed
  cells.
• eg.
• in cardiac infarction SGOT is increased
• in hepatic infection, SGPT is increased above
  the normal levels.

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• II. Oxidative deamination
• It is catalyzed by Amino acid oxidases Occur
  in liver and kidney.
• It includes removal of hydrogen (oxidation) and
  removal of NH3 (deamination).
• There are D- and L-amino acid oxidases that
  oxidizes D- and L-amino acids respectively, to
  the corresponding a-keto acids and the amino
  group is released as ammonia (NH3).

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Oxidative deamination
1
2
?
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• D-amino acid oxidase uses FAD as coenzyme which
  is of limited natural occurance in mammals and of
  high activity,
• L-amino acid oxidase uses FMN as coenzyme which
  is of natural occurrance in mammals, but of low
  activity.

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• III - Non-oxidative deamination
• (direct deamination)
• The a- amino group of serine and threonine
• ( amino acids containing hydroxyl group) can be
  directly converted to NH3 without removal of
  hydrogen.
• This reaction is catalyzed by serine and
  threonine dehydratase which need pyriodoxal
  phosphate as coenzyme.

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Non-oxidative deamination (direct
deamination)
Non-oxidative deamination
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IV .Transdeamination (L-Glutamate dehydrogenase)
Vit B6
NAD NADP
Vit B6
NAD NADP
1
1
1
2
2
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Oxidative deamination
?-ketoglutaric acid
Glutamic acid

• The reaction is both mitochondrial and
  cytoplasmic, occurs mainly in the liver and
  kidney.
• ATP and GTP are allosteric inhibitors while ADP
  and GDP activate the enzyme.
• It is a reversible reaction.

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Metabolism of ammonia

Sources of blood ammonia
Fates of ammonia (Removal of ammonia)
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• Sources of blood ammonia
• 1.From amino acids
• Transdeamination
• Oxidative deamination
• Non-oxidative deamination .
• 2.From glutamine
• Renal glutaminase
• Intestinal glutaminase

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• 3.From amines whether dietary amine or
  monoamine hormones by amine oxidase.
• 4. From catabolism of purines and
• pyrimidines .
• 5.From bacterial action in the intestine either
  from dietary protein residue or from urea
  diffuses into the intestine

• (This is of significance in cases of kidney
  failure )

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• Fates of ammonia (Removal of ammonia)
• Amination of a-ketoacid to form non-essential
  amino acids and other biosynthetic reactions.
• Glutamine synthesis in the brain, liver, muscle
  and renal tissues (4).
• The majority of NH3 (90) will produce urea in
  the liver by urea cycle.
• Excretion in urine upto 1 gm /24 hours urine.
• Traces in blood (up to 100 ug / dl).

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1
4
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Sources and Fates of ammonia
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Glutamine synthesis and ammonia formation
Glutamine synthetase
glutaminase

H2O
ATP ADPp H2O
Glutamic acid
Glutamine
Glutamic acid
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Urea cycle

• Definition
• It is the conversion of ammonia to urea.
• Site
• Mitochondia and cytosol of liver cells only.
• Structure of urea
• O
• H2N - C -NH2
  

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Krebs urea cycleor ornithine cycle for urea
formation

• Urea is formed in the liver mainly ,some in the
  brain and renal tubules from one molecule of CO2
  and two molecules of NH3 using 3 ATP's.
• It is released into the blood with a level of
• 15-40 mg/dL of serum.
• It is the major end product of nitrogen
  catabolism in humans representing 80-90 of the
  nitrogen excreted.

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Urea formation

• 
  NH2
• 3ATP
• CO2 2 NH3 CO
  H2O
• 
  NH2

urea
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• Five reactions each of them utilizes specific
  enzyme in urea cycle.
• The first 2 reactions of urea cycle are
  mitochondrial and the rest 3 reactions are
  cytoplasmic.

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Steps of Urea Cycle
1
2 ATP HCO3- NH3
Carbamoyl phosphate 2 ADP Pi
Pi
Mitochondrion

• .

Ornithine
2
Citrulline
Citrulline
Ornithine
Urea cycle
ATP
Aspartate
3
AMP PPi
Urea
5
Cytosol
H2O
Arginino- succinate
Arginine
4
Fumarate
Oxaloacetate
Malate
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Sources of the Atoms of Urea

• O
• H2N- C -NH2

From Aspartate
From NH3
From Bicarbonate
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mitochondria
cytoplasm
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• Five enzymes of urea cycle
• Carbamoyl phosphate synthase 1
• Ornithine transcarbamoylase (citrulline synthase)
• Argininosuccinate synthetase.
• Argininosuccinase.
• Arginase.

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LINK BETWEEN KREBS' UREA CYCLE AND KREBS'
TRICARBOXYLIC ACID CYCLE
1
2ATP
CO2 NH3
2
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LINK BETWEEN KREBS' UREA CYCLE AND KREBS'
TRICARBOXYLIC ACID CYCLE
Malate
Oxalacetate
Glutamate
a-ketoglutarate
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• 1. The fumarate resulting from reaction
  number 4 (in Krebs urea cycle), under the
  influence of argininosuccinase, undergoes
  conversion to malate by fumarase enzyme.
• This malate forms oxaloacetate by malate
  dehydrogenase. The oxaloacetate undergoes
  Transamination by SGOT to form aspartate.
• This aspartate is needed in urea cycle at
  argininosuccinic synthase enzyme.

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• 2.The CO2 used in urea cycle comes mainly
  from Krebs' tricarboxylic acid cycle.
• The first NH2 group comes from
• L-glutamic acid by L-glutamate
• dehydrogenase.
• The second NH2 group comes from amino group
  of aspartic acid.

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REGULATION OF UREA CYCLE

• 1. Excess ammonia formation stimulates urea
• formation.
• 2. High arginine level stimulates N-acetyl
  glutamate
• synthase enzyme, thus increases urea
  formation.
• 3. High urea level inhibits carbamoylphosphate
• synthase (reaction 1), ornithine
  transcarbamoylase
• (reaction 2) and arginase enzymes
  (reaction 5).
• 4. Carbamoylphosphate synthase is inactive in the
  
• absence of activator, N-acetylglutamate.

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METABOLIC DISORDERS OF UREA CYCLE

• There are five types of congenital
  hyperammonaemia.
• They affect children and manifested by
• 1.vomiting,
• 2.irritability,
• 3.ataxia,
• 4.lethargy coma ,
• 5.mental retardation,and death

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• 1. Hyperammonaemia type I
• It may be due to carbamoylphosphate synthase
  deficiency.
• It causes increase in blood ammonia level
  (normally plasma ammonia is less than 100 µg/dL).
  
• It is a familial disease.

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• 2. Hyperammonaemia type II
• It is due to ornithine transcarbamoylase
  deficiency.
• It is X-chromosome linked deficiency.
• There is increased glutamine in blood, CSF and
  urine due to increased glutamine synthesis as
  consequence of increased tissue levels of
  ammonia.

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• 3. Citrullinaemia type III
• It is due to lack of argininosuccinic synthase .
  
• It is recessive inherited disorder.
• There is an increase in citrulline in plasma, CSF
  and urine.

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• 4. Argininosuccinic aciduria type IV
• It is due to argininosuccinase deficiency.
• It is recessive inherited disorder. There is
  increase in argininosuccinic in plasma, CSF and
  urine.
• It is manifested at age of two years.
• It usually ends in death early in life.

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• 5. Hyperargininaemia type V
• It is due to arginase deficiency.
• There is increase in arginine in blood, CSF and
  urine.
• It affects children ( 1 30,000 ) leading to
  mental retardation ,coma and death.

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Ammonia intoxication(Ammoniacal encephalopathy)

• It is defined as toxicity of the brain due to
  increase in NH3 level in the systemic blood.
• This increased ammonia will be fixed to
• a- ketoglutaric acid to form glutamic acid
  then glutamine leading to interference with
  citric acid cycle so decrease ATP production in
  the brain cells.

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• Causes
• I. Congenital The 5 types of hyperammonaemia
• due to enzymes deficiencies in urea cycle.
• (see urea cycle)
• II. acquired
• 1. Liver disease as cirrhosis due to
  failure
• of urea formation and glutamine
  synthesis.
• 2. Portocaval shunt as in
  bilharziasis.
• 3. Gastrointestinal bleeding by action
  of bacterial
• flora on the blood urea and thus
  NH3 is released
• in large amounts.

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Manifestations of ammonia intoxication

• 1. Tremors
• 2. Blurred vision
• 3. Slurred speech
• 4. Vomiting
• 5. Confusion followed by coma
• and death.

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Treatment

• 1. Injection of Glutamic acid and
  ?-ketoglutaric
• acid
• They act as a carrier for NH3 and combine
  
• with it to form a nontoxic material
  called
• glutamine. Glutamine passes to the
  kidney
• and by glutaminase yielding glutamic acid
• and NH3 excreted in urine as ammonium
  salt.
• (NH4cl).
• 2. Restrict protein diet.

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• 3. Sodium benzoate and phenylacetate
• are given to conjugate with glycine
• and glutamine and rapidly the
• conjugates are excreted in urine.
• 4. Frequent small meals to avoid sudden
• increase in blood ammonia levels.
• 5. Removal of excess NH3 by dialysis in
• acute cases.

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• CATABOLISM OF THE CARBON SKELETON OF AMINO ACIDS

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Catabolism of Amino Acids

• It involves
• I. Removal of the amino acid nitrogen (a-amino
  group) by
• a. Transamination or
• b. Oxidative deamination.
• These two reactions finally produce ammonia and
• aspartate that are the sources of urea nitrogen.
• II. Metabolism of the carbon skeleton of the
  amino acid which includes either
• a. Conversion into glucose, fatty acid or ketone
  bodies or
• b. Oxidation to CO2 and energy.

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Metabolism of Amino Acids
Amino Acid is composed of
AND
Amino group
Carbon skeleton

OR
OR
Converted to Glucose, fat, Or ketone bodies
Oxidized to CO2 Energy
Transferred to a keto acid to form a new amino
acid
Released as ammonia
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Catabolism of the Carbon Skeleton of Amino Acids

• It results in the production of 7 intermediate
• products that directly enter the pathways of
• Intermediary metabolism, resulting either in the
• synthesis of glucose or lipids, or in the
  production
• of energy through their oxidation by the citric
  acid
• cycle.

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Intermediate Products of Amino Acid Catabolism

• These include the following seven intermediate
• products
• 1. Pyruvate.
• 2. ?-ketoglutarate.
• 3. Succinyl CoA.
• 4. Fumarate.
• 5. Oxaloacetate.
• 6. Acetyl CoA.
• 7. Acetoacetyl CoA.

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Glycine Cysteine Serine Alanine Threonine Tryptoph
an
Leucine Lysine Phenylalanine Tyrosine Tryptophan
Glucose
Isoleucine Leucine
Phosphoenol-pyruvate
Pyruvate
Asparagine Aspartate
Acetyl CoA
Acetoacetyl CoA
Oxaloacetate
Tyrosine Phenylalanine
Glutamate Glutamine Histidine Proline Arginine
Fumarate
Citrate
Isoleucine Valine Methionine Threonine
Succinyl CoA
?-keto-glutarate
Fates of the carbon skeletons of amino acids.
Glucogenic amino acids are shaded red, ketogenic
amino acids are shaded green and glucoketogenic
amino acids are shaded blue.
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Glucogenic (glycogenic) Amino Acids

• Definition
• - These are amino acids whose catabolism yields
• pyruvate or one of the intermediates of the
  citric
• acid cycle which are substrates for gluconeo -
• genesis and, therefore, can give rise to the
  net
• formation of glucose or glycogen.
• - They include 14 amino acids.

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Ketogenic Amino Acid

• Definition
• - This is amino acid its catabolism yields to
• either acetoacetate or one of its precursors.
• - Leucine is the only exclusively ketogenic amino
  acid found in proteins because Its carbon
  skeletons is not substrates for gluconeogenesis
  therefore, cannot give rise to the net formation
  of glucose or glycogen.

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Both Glucogenic and Ketogenic (glucoketogenic)
Amino Acids

• Definition
• - These are amino acids whose catabolism yields
  both glucose and ketone bodies.
• - They include 5 amino acids isoleucine, phenyl-
• alanine, tyrosine , tryptophan and lysine
  because part of
• their carbon skeleton can give glucose and the
• other part can give ketone bodies.

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Classification of Amino Acids.
Biological value Ketogenic Glucogenic and ketogenic Glucogenic
Non-essential Tyrosine Glycine Alanine Serine Cysteine Proline Histidine Arginine Aspartate Asparagine Glutamate Glutamine
Essential Leucine Isoleucine Phenylalanine Lysine,Tryptophan Methionine Threonine Valine
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1- Amino Acids That Form Oxaloacetate
Aspartate
Asparagine
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2- Amino Acids That Form ?- Ketoglutarate
Glutamine
Glutamate
Histidine
Proline
Arginine
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3- Amino Acids That Form Pyruvate
Glycine
Serine
Alanine
Tryptophan
Cysteine
Threonine
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Biological functions of Glycine

• 1. Incorporated into proteins.
• 2. Glucogenic amino acid.
• 3. Source of energy.
• 4. Formation of serine.
• 5. Formation of bile acids (e.g. glycocholate).
• 6. Formation of Glutathione (GSH) which is a
  tripeptide formed of glutamate, cysteine and
  glycine.
• 7. Formation of Heme (succinyl COA Glycine).
• 8. Formation of purines.
• 9. Formation of creatine (synthesized from
  glycine, arginine and methionine).
• 10. Detoxification of Benzoic acid (food
  preservatve) by converting it into hippuric acid
  which is excreted in urine

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Biological Functions of Cysteine

• 1. Incorporated into proteins.
• 2. Glucogenic amino acid.
• 3. Source of energy.
• 4. Formation of taurine (a component of the bile
  acid taurocholate).
• 5. Formation of Glutathione.

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Biological Functions of Tryptophan

• 1. Formation of niacin.
• - It is a member of vitamin B complex
• - it is a component of NAD and NADP.
• 2. Formation of serotonin.
• - It is a neurotransmitter that controls the
  mood.
• - It is a vasoconstrictor substance.
• - It causes contraction of smooth muscles of
• bronchi and intestine.
• 3. Formation of melatonin.
• - It induces sleep.
• - It is an antioxidant.
• - It causes hypopigmentation.

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4- Amino acids that form Fumarate
Phenylalanine
Tyrosine
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Functions of Phenylalanine and Tyrosine

• 1. Synthesis of catecholamines
• a. Adrenaline (epinephrine).
• b. Noradrenaline (norepinephrine).
• c. Dopamine.
• 2. Synthesis of thyroid hormones
• a. Tri-iodothyronine (T3).
• b. Tetra-iodothyronine (T4, thyroxine).
• 3. Synthesis of melanin pigments.
• 4. Synthesis of tissue proteins.
• 5. Source of energy.

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Phenylalanine hydroxylase
Phenylalanine
Tyrosine
?-KG
O2
H2O
Phenylketonuria
Tyrosine transaminase
PLP
Glu
P-Hydroxyphenyl-pyruvate hydroxylase
Homogentisate
P- Hydroxyphenyl pyruvate
Ascorbate Cu2
O2
CO2
O2
Homogentisate dioxygenase
Alkaptonuria
Maleylacetoacetatecis- trans isomerase
Ascorbate
Fe2
Maleylacetaoacetate
Fumarylacetoacetate
Fumarylacetoacetate hydrolase
GSH
H2O
Acetoacetate
Fumarate
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Characteristics of Phenylketonuria

• 1. phenylalanine in blood, urine, and tissues.
• 2. phenylpyruvate, phenylacetate
  phenyllactate in urine musty
  (mousey) odor of urine.
• 3. CNS manifestations
• a. Mental retardation (low IQ) by the age of 1
  year
• due to the toxic effects of phenylalanine
  possibly
• on the transport and metabolism of other
  aromatic
• amino acids (as tyrosine and tryptophan) in the
• brain resulting in deficiency of
  neurtransmitters
• such as catecholamines and serotonin.
• b. Failure to grow, walk or talk.
• c. Seizures, tremors, hyperactivity
  microcephaly.

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• 4. Hypopigmentation
• - It is due to competitive inhibition of
  tyrosinase ( that catalyzes the first step
  in the formation of melanin pigment from
  tyrosine) by the high level of phenylalanine.
• -There is fair hair, light skin color, and blue
  eyes.

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Diagnosis of Phenylketonuria

• A. Neonatal diagnosis
• - Infants with PKU frequently has normal blood
• phenylalanine level at birth because the mother
• clears the increased blood phenylalanine in her
• affected fetus through the placenta thus showing
• false negative results.
• - There is blood phenylalanine level in newborn
  fed
• with breast milk or formula for 48 hours.
• B. Antenatal diagnosis
• - It is done by in vitro detection of PKU gene
• mutation in cells of amniotic fluid.

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Treatment of Phenylketonuria

• - It must begin during the 7-10 days of life to
  prevent
• mental retardation.
• - Treatment involves the following
• 1. Feeding a diet low in phenylalanine at least
  till the
• age of 8 years or better life-long to keep
  blood
• phenylalanine within the normal range. This
  diet
• includes synthetic amino acid preparations and
  
• natural foods low in their phenylalanine
  content
• such as fruits, vegetables and certain cereals.
• 2. Supplementation with tyrosine that becomes an
• essential amino acid in classic PKU.

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Alkaptonuria

• It is a rare autosomal recessive metabolic
  disease.
• Cause
• Deficiency of homogentisate dioxygenase
  (oxidase).
• Characteristics
• 1. Elevated level of homogentisic acid in urine
• (homogentisic aciduria) which is oxidized to a
  dark
• pigment on standing giving urine a black color.
• 2. Large joint arthritis.
• 3. Black pigmentation of cartilage and
  collagenous
• tissue.
• Treatment
• Giving diet low in phenylalanine and tyrosine to
• reduce the level of homogentisic acid.

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Albinism

• Cause
• Deficiency of tyrosinase that is involved in the
• synthesis of melanin pigments.
• Manifestations
• Absence of melanin pigments from hair, iris of
  eyes,
• and skin results in
• a- Fair (blond) hair, white eyebrows and lashes.
• b- white color of the iris that reflects the red
  color of blood vessels of the retina behind.
• c- Photophobia.
• d- Skin burns and skin cancer.

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Synthesis of Melanin Pigments

Melanin pigments
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5- Amino acids that form succinyl CoA
Methionine
Threonine
Valine
Isoleucine
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Methionine

• - It is a sulfur-containing amino acid.
• - Function
• 1. Formation of s-adenosyl methionine (SAM) which
  is a methyl donor.
• 2. Formation of cysteine.
• 3. Incorporated into proteins.
• 4. Glucogenic amino acid.
• 5. Source of energy.

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• CONVERSION OF AMINO ACIDS TO SPECIALIZED PRODUCTS

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Specialized Products of Amino Acids

• A. Glycine gives rise to the following products
• 1. Porphyrins.
• 2. Creatine.(It is present in muscle as creatine
  phosphate (CP)
• which is a high-energy phosphate compound
• 3. bile acids and salts.
• 4. Hippuric acid
• B. Phenylalanine and tyrosine give rise to the
  following
• products
• 1. Catecholamines.
• 2. Thyroid hormones.
• 3. Melanin.
• C. Tryptophan gives rise to the following
  products
• 1. Niacin (nicotinic acid, vitamin B3).
• 2. Serotonin.
• 3. Melatonin.

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• D. Histidine gives rise to the following
  products
• 1. Histamine.
• E. Glutamate gives rise to the following
  products
• 1. Glutathione (GSH).
• 2. Gamma amino butyric acid (GABA, inhibitory
  neurotransmitter).
• F. Aspartate gives rise to the following
  products
• 1. ß- alanine.( component of CoA )
• G. Arginine gives rise to the following products
• 1. Nitric oxide.

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Nitric Oxide (NO)

• Synthesis
• Function
• 1. Neurotransmitter.
• 2. Vasodilator.
• 3. Inhibitor of platelet aggregation.

NH2 C NH NH CH2
CH2 H2NCH COOH Arginine
NH2 C O NH
CH2 CH2 H2NCH COOH Citrulline
Nitric oxide synthase (NOS)
NO

NADPH FAD O2
NADP FADH2