Synthesis of non-essential amino acids

Dr. Sarray Sameh

 TYPES OF AMINO ACIDS

• Amino acids that cannot be synthesized by the human body and are required to
be taken in the diet are referred to as essential amino acids.

• Amino acids that can be synthesized by the human body and can or cannot be
taken in the diet are referred to as non-essential amino acids.

• Both essential and non-essential amino acids can be grouped into glucogenic,
ketogenic or both.
Biosynthesis of non-essential aminoacid

• Non-essential amino acids are synthesized

from:
– Intermediates of metabolism

– Or, as in the case of tyrosine and cysteine, from

the essential amino acids phenylalanine and
methionine respectively
 A- synthesis of ketoacids
• Alanine, aspartate and
glutamate are synthesized by
transfer of an amino group to
the a-ketoacids pyruvate,
oxaloacetate and a-
ketoglutarate, respectively

• These transamination
reactions are the most direct
of the biosynthetic pathways

• Glutamate is unusual in that it

can be synthesized by the
reductive amination
catalysed by GDH
B- synthesis by amidation

1. Glutamine:
➢Contains an amide linkage with
ammonia at the g-carboxyl,
➢is formed from glutamate by
glutamine synthetase
➢Requires ATP

➢In addition to producing glutamine

for protein synthesis, the reaction
also serves as major mechanism for
the detoxification of ammonia in
brain and liver
 B- Synthesis by amidation
2. Asparagine
➢Contains an amide linkage
with ammonia at the b-
carboxyl
➢Is formed from aspartate by
asparagine synthetase using
glutamine as the amide donor
➢The reaction requires ATP
 C. Proline synthesis
• Glutamate is converted to proline by cyclisation
and reduction reactions
 D. Serine, Glycine & Cysteine
1. Serine:
➢ arises from 3-phosphoglycerate, an intermediate in glycolysis, which
is first oxidized to 3-phosphopyruvte and then transaminated to 3-
phosphoserine
➢ Serine is formed by hydrolysis of the phosphate ester

➢Serine can also be formed from

Glycine through transfer of a
hydroxymethyl group by serine
hydroxymethyl transferase
 D. Serine, Glycine & Methionine

2. Glycine:
• Is synthesized from serine by removal of a
hydroxymethyl group by serine hydroxymethyl
transferase
 D. Serine, Glycine & Methionine
3. Cysteine: is synthesized by two
consecutives reactions in which
homocysteine (derived from
methionine) combines with serine,
forming cystathionine, which in turn,
is hydrolysed to a-ketobutyrate and
cysteine
Because methionine is an essential
amino acids, cysteine synthesis can
be continued ONLY if the dietary
intake of methionine is adequate
 E. Tyrosine
• Tyrosine is formed from phenylalanine (essential AA) by
phenylalanine hydroxylase.

• The reaction requires molecular oxygen and the coenzyme BH4 which
can be synthesized from GTP by the body.

• Tyrosine, like cysteine, is formed from an essential amino acid and is,
therefore, this AA is non essential only when there is an adequate
supply of essential AA phenylalanine.
 Metabolic defect in amino acids metabolism
➢Inborn errors of metabolism are commonly caused by mutant genes that
generally result in abnormal proteins, most often enzymes.

➢The inherited defects may be expressed as total loss of enzyme activity or as

a partial deficiency in catalytic activity

➢The inherited defects of amino acid metabolism result in mental retardation

or other developmental abnormalities

➢they constitute a very significant portion of pediatric genetic diseases

➢Phenylketonuria (PKU) is the most important disease of amino acid

 Phenylketonuria
(PKU)
• PKU is caused by a deficiency
of phenylalanine hydroxylase.
• Is the most common inborn
metabolic disease
• Biochemically it is
characterized by accumulation
of phenylalanine (and a
deficiency of tyrosine).
• New born Screening of is
possible
 Characteristics of PKU
• Elevated phenylalanine:
– Phe is present in elevated concentrations in tissues, plasma and urine.
– Phenyllactate, phenylacetate and phenylpyruvate which are not
normally produced in significant amounts in the presence of
phenylalanine hydroxylase are also elevated in PKU. These metabolites
give urine a characteristic musty odor.

• CNS symptoms: mental retardation (rarely achieve an Intelligence

Quotient (IQ) greater than 50), failure to walk or talk, seizures,
hyperactivity, tremor, failure to grow ..

• Hypopigmentation: patients with PKU often show a deficiency of

pigmenation: abinism (fair hair, light skin color and blue eyes); The
hydroxylation of tyrosine by tyrosinase which is the first step in the
formation of the pigment melanin, is competitively inhibited by
the high levels of phenylalanine present in PKU
END!