Biosynthesis of

phenyl alanine,
tyrosine
tryptophan .

Presentation by : GOPIKA.O
 All amino acids are derived from intermediates in glycolysis, citric
acid cycle or pentose phosphate pathway.
 Nitrogen enters these pathways by way of Glutamate &
Glutamine.
 Synthesis of aromatic amino acids involves a complex pathway .
 Aminoacids are biosynthetically produced from corresponding
metabolic precursors – Phosphoenol pyruvate & Erythrose-4-
phosphate.
 And the pathway is often referred to as “Shikimate pathway”;
that leads to the formation of chorismate ,which is the ultimate
precursor of Phe, Tyr, Trp (Aromatic amino acids).
 These aromatic amino acids are also the derivatives of many
secondary metabolites- essential for growth, metabolism, &
production of certain compounds like Salicylate & auxin.
 NOTES : All carbons are derived from either Erythrose-4-
phosphate / PEP.
 Step:6 is competitively inhibited by a most widely used herbicide
GLYPHOSATE (-COO-CH2-NH-CH2-PO3˄2-), which is non-toxic to
mammals which lacks this biosynthetic pathway.
 The chemical nams QUINATE, SHIKIMATE, & CHORISMATE- are
derived from the names of plants in which the intermediates
have been found to accumulate.
 Synthesis of chorismate, a key intermediate
in the synthesis of the aromatic amino acids.
. All carbons are derived from either
erythrose-4-phosphate (purple) or
phosphoenolpyruvate (red).
The pathway enzymes are:
(l) 2-keto-3-deoxy- D-arabinoheptulosonate-7-
phosphate synthase
(2) dehydroquinate synthase
(3) 5-dehydroquinate dehydratase,
(4) shikimate dehydrogenase
(5) shikimate kinase3-
enoylpyruvylshikimmate-5phosphate
synthase
(7) chorismate synthase.

Note :step (2) requires NAD+ as a cofactor,

and NAD+ is released unchanged.

It may be transiently reduced to NADH during

the reaction, to produce an oxidized reaction
intermediate.
 Chorismate is a key intermediate in the syntheis of Trp, Phe, Tyr.
PEP
+
ERYTHROSE-4-PHOSPHATE

phe tyr trp

tyr
 Aromatic amino acids are not readily available in the environment,
even though the benzene ring is very stable.
 The Branched pathway to Trp, Tyr, Phe occuring in bacteria, fungi, &
plants- is the main biological route of aromatic ring formation.
 It proceeds through ring closure of an aliphatic precursor followed
by stepwise addition of double bonds.
 First four steps produce Shikimate, A seven-carbon molecule
derived from erythrose-4-phosphate & PEP.
 Shikimate is converted to chorismate in 3 steps that include –
addition of three more carbons from a molecule of PEP.
 Chorismate is the first branch point of the pathway with one branch
leading to Trp & the other to Tyr & Phe.
 In the Trp branch , chorismate is converted to anthranilate in a
region in which Glutamine donates the nitrogen that will become
part of the indole ring.
 Anthranilate then condenses with PRPP.
 The indole ring of Trp is derived from the ring carbons & amino grp
of anthranilate plus two carbons derived from PRPP.

 The final reaction in the sequence is catalysed by Tryptophan

Synthase.

 This enzyme has α2β2 subunit structure & can be dissociated into
two α-subunit & β2 subunits that catalyse different parts of the
overall reaction.
Indole-3-Glycerol Phosphate Indole + G-3-P
α-subunit

Indole + Serine Tryptophan + H2O

Beta-2 - subunit

Biosynthesis of Tryptophan from chorismate in

bacteria & plants.
 In E coli , enzymes catalysing step 1 ( anthranilate synthase ) &
step 2 ( anthranilate phosphoribosyl transferase) – are subunits
of a single complex.
 Enzymes are :
1. Anthranilate
synthase.

2. Anthranilate
phosphoribosyl
transferase.

3. N-( 5’-
phosphoribosyl )-
anthranilate
isomerase.

4. Indole -3 – glycerol
phosphate synthase.

5. Tryptophan
synthase.
 The second part of the reaction requires Pyridoxal Phosphate .
 Indole formed in the first part is not released by the enzyme ,
but instead moves through a channel from the α-subunit active
site to β- subunit active site, where it condenses with schiff base
intermediate derived from Serine & PLP.
 Intermediate channelling of this type is a major feature of the
entire pathway from chorismate to Trp.
 Enzyme active sites catalysing different steps of the pathway to
tryptophan are found on single polypeptides in some species of
fungi & bacteria, but are separate proteins in others.
 In addition , the activity of some of these enzymes requires a non-

covalent association with other enzymes of the pathway.

 Thus , all the pathway enzymes are components of a large, multi-

enzyme complex, in both prokaryotes & eukaryotes.

 Such complexes are generally not preserved intact when the

enzymes are isolated using traditional biochemical methods.

 Thus, on concluding , it is evident that the biosynthesis of aromatic

amino acids are complex as compared to other aliphatic amino

acids.
 Biosynthesis of Phe & Tyr from chorismate in bacteria
& Plants
Enzymes are :
• Chorismate
mutase .

• Prephenate
dehydrogenase.

• Prephenate
dehydratase.
 Conversion of chorismate to prephanate a rare
biological example of a claise rearrangement.
 In plants & bacteria , phenylalanine & tyrosine are sy nthesised
from chorismate in pathways much less complex than the
tryptophan pathway.
 The common intermediate is prephenate.
 The final step in both cases is transmination is glutamate.
 Animals can produce tyrosine directly from Phe through
hydroxylation at C-4 of the phenyl group by Phenylalanine
hydroxylase; this enzyme also participates in the degradation of
phenylalanine.
 Tyrosine is considered a conditionally esential amino
acid , or as non- essential so far as it can be synthesised
from th essential amino acid phenylalanine.
 Reference
 Lehninge
 Principles of Biochemistry

Fourth edition
David. L. Nelson
Michael. M. Cox
Page : no : 848-851