Lakhasly

Dr.Prompt replacement of dietary protein by an amino acid mixture that lacks leucine, isoleucine, and valine averts brain damage and early mortality.Amar Babikir Elhussein BSc, MSc & PhD Biosynthesis of Nonessential Amino acids and Fate of Amino Acid Carbon Skeleton Introduction: ?The major product of degradation of the carbon skeleton of the amino acids are pyruvate, intermediate of TCA cycle acetyl CoA and acetoacetate.Methionine: provide methyl group for synthesis of various compounds, it sulfur is incorporated into cysteine; and the remaining carbon form Succinyl CoA.The amino acids that are synthesized from intermediate of glycolysis are degraded to pyruvate ( Serine, Glycine, Cysteine and alanine).Four amino acids converted to Propionyl CoA, Which carboxylated in reaction require Biotin to form Methylmalonyl CoA, Which is rearranged to form Succinyl CoA in reaction require vitamin B12.Plasma and urinary levels of leucine, isoleucine, valine, ?-keto acids, and ?-hydroxy acids (reduced ?-keto acids) are elevated.The enzymes glutamate dehydrogenase, glutamine synthetase, and aminotransferases occupy central positions in amino acid biosynthesis.When the amino acid is degraded, the major products are Pyruvate, Intermediate of TCA cycle, acetyl CoA or Acetoacetate.Tyrosine: Obtained from the diet or by hydroxylation of phenylalanine, is converted to Homogentisate, whose aromatic ring is opened and cleaved, forming fumarte.3) Glycine and cysteine: Can be derived from Serine Serine biosynthesis II. Amino acid derived from TCA cycle: 1.?Arginine can produced in urea cycle via Ornithine which is produced by transamination of Glutamate semialdehyde.As the name implies, the odor of urine in maple syrup urine disease (branched-chain ketonuria) suggests maple syrup or burnt sugar.Ten of the nonessential amino acids contain carbon skeleton that may be derived from glucose.Four amino acids (Lysine, Threonine, Isoleucine and tryptophan), Can form acetyl CoA ?Of the 20 amino acids commonly found in proteins, 11 are not essential in the adult diets because it can be synthesized in the body.Intermediate of glycolysis serve as precursor for Serine, glycine, cysteine and alanine.B. Proline and Arginine are derived from Glutamate semialdehyde which is formed by reduction of Glutamate.The eleven nonessential amino acid is synthesized by hydroxylation of the essential amino acid Phenyl alanine.Activity II catalyzes reduction of dihydrobiopterin by NADPH, and activity I the reduction of O2 to H2O and of phenylalanine to tyrosine.Glycine: in a reversal of the reaction utilized for it synthesis, react with Methylene tetrahydrofolate to form serine.ii. Amino acids that are converted to intermediate of TCA cycle: ?Carbons from 4 groups of amino acids from TCA cycle intermediates, ?Valine and Isoleucine: two of three branched chain amino acids, Form Succinyl CoA.i. Valine is eventually converted to Succinyl CoA via Propionyl CoA and Methylmalonyl CoA.ii. Isoleucine is converted to Succinyl CoA after two of it carbon are released as acetyl CoA.Tyrosine: ?- Ketoglutarate.?????2.3.4.???1.2.3.4.2.4.5.6.1.2.??3.2.3.2.??????

Dr. Amar Babikir Elhussein
BSc, MSc & PhD
Biosynthesis of Nonessential Amino acids
and Fate of Amino Acid Carbon Skeleton
Introduction:
 Of the 20 amino acids commonly found in proteins, 11 are not essential in
the adult diets because it can be synthesized in the body.
 Ten of the nonessential amino acids contain carbon skeleton that may be
derived from glucose.
 The major product of degradation of the carbon skeleton of the amino acids
are pyruvate, intermediate of TCA cycle acetyl CoA and
acetoacetate.
 The enzymes glutamate dehydrogenase, glutamine
synthetase, and aminotransferases occupy central
positions in amino acid biosynthesis.
❑Glutamate and Glutamine.
 Reductive amination of α-ketoglutarate is catalyzed by
glutamate dehydrogenase.
 Amination of glutamate to glutamine is catalyzed by
glutamine synthetase.
The glutamine synthetase reaction.
The glutamate dehydrogenase

1. Amino acids derived from Glycolysis:
    Intermediate of glycolysis serve as precursor
   for Serine, glycine, cysteine and alanine.

1. Alanine:
   Can be derived from pyruvate by
   transamination.


2. Serine:
   Can be synthesized from 3-
   phosphoglycerate.


3. Glycine and cysteine:
   Can be derived from Serine
   Serine biosynthesis
   II. Amino acid derived from TCA cycle:

1. Aspartate can be derived from
   oxaloacetate by transamination.


2. Asparagine is produced from aspartate
   by amidation.


3. Glutamate can be derived from α-
   Ketoglutarate by Transamination or by
   Glutamate dehydrogenase.
   The asparagine synthetase reaction.


4. Glutamine, Proline and Arginine can be derived
   from Glutamate.
   A. Glutamine is produced by amidation of glutamate.
   B. Proline and Arginine are derived from Glutamate
   semialdehyde which is formed by reduction of
   Glutamate.
   ❖Proline is produced by cyclization of Glutamate semi
   aldehyde.
   ❖Arginine can produced in urea cycle via Ornithine
   which is produced by transamination of Glutamate
   semialdehyde.
   
   Biosynthesis of Proline from glutamate
   III. Tyrosine:
    The eleven nonessential amino
   acid is synthesized by
   hydroxylation of the essential
   amino acid Phenyl alanine.
   The phenylalanine hydroxylase reaction.
   Two distinct enzymatic activities are involved.
   Activity II catalyzes reduction of dihydrobiopterin by
   NADPH, and activity I the reduction of O2 to H2O and
   of phenylalanine to tyrosine.
   ❑Degradation of amino acids
    When the amino acid is degraded, the major products are Pyruvate,
   Intermediate of TCA cycle, acetyl CoA or Acetoacetate.
    Amino acid form Pyruvate or intermediate of TCA cycle in the liver are
   glucogenic.
    Amino acid form Acetyl CoA or Acetoacetate are Ketogenic.
   
    Some amino acids are both glucogenic and ketogenic.
   i. Amino acids that are converted to pyruvate:
    The amino acids that are synthesized from intermediate of glycolysis are
   degraded to pyruvate ( Serine, Glycine, Cysteine and alanine).


5. Serine: Is converted to pyruvate and NH4

• by serine dehydratase.

2. 
   

   Glycine: in a reversal of the reaction utilized for it synthesis, react with
   Methylene tetrahydrofolate to form serine.

   
   


3. 
   

   Cysteine: forms pyruvate. Its sulfur
   form H2SO4.

   
   


4. 
   

   Alanine: Can be transaminated to
   pyruvate.
   ii. Amino acids that are converted to intermediate of TCA cycle:
    Carbons from 4 groups of amino acids from TCA cycle intermediates, α –
   Ketoglutarate, Succinyl CoA, Fumarate and Oxaloacetate.
   A. Amino acids related to Glutamate can form α – Ketoglutarate by
   transamination:

   
   


5. 
   

   Glutamine: Can be converted by Glutaminase to Glutamate with release
   of amide group as NH4.

   
   


6. 
   

   Proline: Can be oxidized then ring is opens and Glutamate is formed.

   
   


7. 
   

   Arginine: Can be cleaved by arginase in the liver to form Urea and
   Ornithine. Ornithine can be transaminated to Glutamate semialdehyde,
   Which can be oxidized to Glutamate.

   
   


8. 
   

   Histidine: Can be converted to Formiminoglutamate (Figlu).
   The formimino group is transferred to tetrahydrofolate (FH4) and the
   remaining five carbon form Glutamate.

   
   


9. 
   

   Glutamate: Can be deaminated by Glutamate dehydrogenase or
   transaminated to form α – Ketoglutarate.
   B. Amino acids related to Glutamate can form Succinyl CoA by
   transamination:
    Four amino acids converted to Propionyl CoA, Which carboxylated in
   reaction require Biotin to form Methylmalonyl CoA, Which is rearranged
   to form Succinyl CoA in reaction require vitamin B12.

   
   


10. 
    

    Threonine: is converted by dehydratase to NH4

    
    

• and α – Ketobutyrate,
  which is oxidatively decarboxylated to Propionyl CoA.
  ✓In deferent reaction, threonine maybe converted to glycine and acetyl CoA.

2. Methionine: provide methyl group for synthesis of various compounds, it
   sulfur is incorporated into cysteine; and the remaining carbon form
   Succinyl CoA.
   ✓ Methionine and ATP Form S- Adenosylmethionine (SAM), Which
   donate Methyl group and form Homocycteine.
   ✓ Homocysteine can react with serine and form cystathionine, which is
   cleaved and produce cystien ,NH4
   +, and α – Ketobutyrate which
   converted to Propionyl CoA.


3. Valine and Isoleucine: two of three branched chain amino acids, Form
   Succinyl CoA.
   i. Valine is eventually converted to Succinyl CoA via Propionyl CoA and
   Methylmalonyl CoA.
   ii. Isoleucine is converted to Succinyl CoA after two of it carbon are
   released as acetyl CoA.
   C. Amino acids that form Fumarate:


4. Phenylalanine: Is converted to tyrosine by phenylalanine
   hydroxylase.


5. Tyrosine: Obtained from the diet or by hydroxylation of phenylalanine,
   is converted to Homogentisate, whose aromatic ring is opened and
   cleaved, forming fumarte.


6. Aspartate: Is converted to Fumarate via reaction of urea cycle.
   D. Amino acids that converted to Oxaloacetate:


7. Aspartate: is transaminated to form Oxaloacetate.


8. Asparagine: loses it amid group NH4

• in reaction catalyzed by
  Asparaginase forming Aspartate.
   iii. Amino acid converted to acetyl CoA or Acetoacetate
   Four amino acids (Lysine, Threonine, Isoleucine and tryptophan), Can
  form acetyl CoA
   phenylalanine and tyrosine form acetoacetate.
  ❑METABOLIC DISORDERS OF BRANCHEDCHAIN AMINO ACID CATABOLISM:
   As the name implies, the odor of urine in maple syrup urine disease (branched-chain
  ketonuria) suggests maple syrup or burnt sugar.
   The biochemical defect involves the -keto acid decarboxylase complex.
   Plasma and urinary levels of leucine, isoleucine, valine, α-keto acids, and α-hydroxy acids
  (reduced α-keto acids) are elevated.
   The mechanism of toxicity is unknown.
   Early diagnosis, especially prior to 1 week of age, employs enzymatic analysis.
   Prompt replacement of dietary protein by an amino acid mixture that lacks leucine,
  isoleucine, and valine averts brain damage and early mortality.