The glutamate family :-
Conversion of a-Ketoglutarate to Glutamate
In the presence of enzyme glutamate dehydrogenase.
Synthesis of Glutamine -two step process.
Synthesis of Proline
Synthesis of Arginine- more complex pathway
2. BIOSYNTHESIS DERIVATION OF AMINO ACID FAMILY
α- KETOGLUTARATE GLUTAMATE GLUTAMINE
ARGININE
PROLINE
GLUTAMATE FAMILY
OXALOACETATE ASPARTATE ASPARAGINE
METHIONINE
THREONINE
ISOLEUCINE
LYSINE
3- PHOSPHOGLYCERATE SERINE GLYCINE
CYSTEINE
SERINE
RIBOSE-5-PHOSPHATE + ATP HISTIDINE
3. Glutamic acid is the main pathway for assimilation of
ammonia by reductive amination of a-ketoglutaric acid
catalyzed by glutamic acid dehydrogenase using NADPH2 as
reductant
Glutamic acid
α- KETOGLUTARIC ACID
amino transferase
a-ketoglutaric acid
Glutamic acid
STEP-1
4. Three other amino acids belonging to the glutamic
acid family are synthesized in other ways.
These are:
1.Glutamine (an amide),
2. Proline and
3.Arginine.
5. 1. GLUTAMINE
Glutamine is synthesized by the enzyme glutamine synthetase
which requires ATP. An enzyme- bound glutamyl phosphate acts
as an intermediate which reacts with ammonia to produce
glutamine.
Glutamine
Glutamic acid
Glutamate
synthetase
Glutamate
kinase
6. 2.PROLINE:
proline is a heterocyclic amino acid. It is synthesized via the intermediates, glutamic
acid semi-aldehyde and pyrroline 5-carboxylic acid. Glutamic acid is reduced by an
nadh2-linked dehydrogenase to glutamic acid semi-aldehyde which undergoes
spontaneous cyclization to form pyrroline 5-carboxylic acid.
pyrroline 5-carboxylic acid
PROLINE
glutamic acid semi-
aldehyde
Glutamic acid
Glutamate
dehydrogenase
Proline carboxylate
reductase
Non enzymatic
7. 3.ARGININE
• Arginine biosynthetic pathway is more complex. It is synthesized from glutamic acid via
two non-protein amino acids — ornithine and citrulline. The steps from glutamic acid to
ornithine, from ornithine to citrulline and from citrulline to Arginine are described
separately
• It can be seen that ornithine differs from glutamic acid in having an extra amino (NH2
–)
group attached to the y-carbon atom. This amino group is donated by another molecule
of glutamic acid which is thereby deaminated to α-ketoglutaric acid.
• The first step consists of condensation of acetyl CoA and glutamic acid forming n-acetyl
glutamic acid with release of free coenzyme a. In the next two steps, phosphorylation by
ATP and reduction occur to yield n-acetyl glutamyl semi-aldehyde which by amination
forms n-acetyl ornithine. In the last step, n-acetyl ornithine yields ornithine by removal of
acetic acid and addition of water.
9. Ornithine produced by the above pathway next reacts with carbamyl phosphate to
produce citrulline. In bacteria, carbamyl phosphate is synthesized from CO2,
NH3 and ATP by the enzyme carbamyl phosphate synthetase.
carbamyl
phosphate
Citrulline
synthetase
10. Finally, citrulline is converted to arginine in two steps. The first step consists of condensation of citrulline with aspartic acid requiring
ATP to form arginine succinic acid. The reaction is catalysed by arginine-succinate synthetize. ATP supplies the energy for
condensation and is hydrolysed to AMP and pyrophosphate.
The product of the synthetase reaction is next cleaved into arginine and fumaric acid
citrulline
Arginine
Aspartic
acid
Arginine
succinic acid