Pharmacognosy and Phytochemistry II, acetate Pathwa, shikimic acid pathway, and amino acid pathway

1. Acetate pathway
NGSPM COP, Nashik
Pharmacognosy and Phytochemistry II
By:- Mr. Rohit Pradip Mali
❖Acetate Pathway :
Acetate-Mevalonate Pathway: Since a long time biochemists were
aware of the involvement of acetic acid in the synthesis of
cholesterol, squalene and rubber like compounds. The discovery
of acetyl co-enzyme A called as And 'active acetate' in 1950,
further supported the role of acetic acid in biogenetic pathways.
Later, mevalonic acid was found to be associated with the
acetate. Mevalonic acid further produced isopentenyl
pyrophosphate (IPP) and its isomer Dimethylallyl
pyrophosphate (DMAPP). These two main intermediates IPP
and DMAPP set the 'active isoprene unit as a basic building
block of isoprenoid compounds. Both of these units yield
geranyl pyrophosphate (C- monoterpenes) which further
association with IPP produces farnesyl pyrophosphate (C,-
sesquiterpenes)
Farnesyl pyrophosphate with one more unit of IPP develops into
geranyl- geranyl pyrophosphate (C20-diterpenes). The farnesyl
pyrophosphate multiplies with its own unit to produce squalene
and its subsequent cyclization gives rise to

2. cyclopentanoperhydrophenantherene skeleton containing
steroidal compounds like cholesterols and other groups like
triterpenoids. The acetate mevalonate pathway thus works
through PP and DMAPP via squalene to produce two different
skeleton containing compounds i.e.steroids and triterpenoids. It
also produces vast array of monoterpenoids, sesquiterpenoids,
diterpenoids,carotenoids, polyprenols and also the compounds
like glycosides and alkaloids in association with other pathways
(Fig. below).

4. Malonate Pathways: Acetate pathway operates functionally
with the involvement of acyl carrier protein (ACP) to yield fatty
acyl thioesters of ACP These acyl thioesters forms the important
intermediates in fatty acid synthesis. These C2 acetyl CoA units
at the later stage produces even mumber of fatty acids from n-
tetranoic (butyric) to n-ecosanoic (arachidic acid). The synthesis
of fatty acids is thus explained by the reactions given in
(Fig below)
Unsaturated fatty acids are produced by subsequent direct
dehydrogenation of saturated fatty acids. Enzymes play
important role in Vol governing the position of newly
introduced double bonds in the fatty acids.

6. ❖ Shikimic Acid Pathway :
• The shikimic acid pathway is a metabolic pathway
for the biosynthesis of aromatic amino acids
(phenylalanine, tyrosine and tryptophan).
• The shikmic acid is a key intermediate from carbohydrate for the
biosynthesis of C6-C3 units (phenyl propane derivative).
• The seven enzymes involved in the shikimate
pathway are DAHP synthase, 3-dehydroquinate
synthase, 3-dehydroquinate dehydratase, shikimate
dehydrogenase, shikimate kinase, EPSP synthase,
and chorismate synthase.
• The pathway starts with two substrates, phosphoenol pyruvate
and
erythrose-4-phosphate and ends with chorismate,
• A substrate for the three aromatic amino acids.
1. The pathway starts with two substrates, phosphoenol
pyruvate and erythrose-4-phosphate and ends with
chorismate, a substrate for the three aromatic amino
acids.
3. The fifth enzyme involved is the shikimate kinase,
an enzyme that catalyzes the ATP-dependent
phosphorylation of shikimate to form shikimate
3-phosphate (shown in the figure below).

8. 4. Shikimate 3-phosphate is then coupled with phosphoenol
pyruvate to give 5 enolpyruvylshikimate-3-phosphate via the
enzyme 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase.
Then 5-enolpyruvylshikimate-3-phosphate is transformed into
chorismate by a chorismate synthase. Prephenic acid is then
synthesized by a Claisen rearrangement of chorismate by
chorismate mutase. Prephenate is oxidatively decarboxylated
with retention of the hydroxyl group to give p-
hydroxyphenylpyruvate, which is transaminated using glutamate
as the nitrogen
L source to give tyrosine and a-ketoglutarate.
The prephanic acid undergo aromatization to synthesize
Phenylpyruvic acid followed by reductive amination to form
Phenylalanine.
The anthranilic acid from chorismic acid extended to form
phosphoribosylanthranilic aicd. Later in conjugation with serine
in presence of tryptophan synthase it converts to aromatic acid
tryptophan.

9. ❖ Amino Acid Pathway :
In plants amino acids are formed and found in the free state
or as the fundamental units of proteins. Some aromatic amino
acids like that of phenylalanine, tyrosine and tryptophan are
biosynthesized via shikimic acid pathway. The aliphatic and
heterocyclic amino acids have some different route of
biogenesis. Nitrogen enters in the metabolic reactions by
reductive amination of a-keto acids like pyruvic, oxaloacetic and
a- ketoglutaric acids to afford the aliphatic amino acids like
alanine, aspartic acid and glutamic acid respectively (Fig below)

11. Glutamic acid becomes a precursor for arginine and
proline (fig below)

12. 3- Phosphoglyceric acid produces an amino acid serine which
can be readily converted to glycine
Methionine is biosynthesized from cysteine and homoserine, a
4- carbon compound source via homocysteine intermediate

13. Amino acids like Alanine, Valine, Leucine, and Isoleucine are
derived from pyruvates (Fig below).
Peptides and proteins are biosynthesized from the amino acids.
The molecules of amino acids gets condensed with each other by
forming a peptide linkage to form dipeptide, tripeptide and
subsequently polypeptide with more than three amino acids.
Protein synthesis generally takes place in association with the
ribosomes present in the endoplasmic reticulum