Transcript File

The Metabolic Pathway of
Shikimic Acid
Aromatic Amino Acids
Phenolic Compounds
Jan Michael O. Santos
Philippine Normal University
College of Science
Department of Physical Sciences
Outline of Discussion
1. Shikimic Acid Pathway
a.
b.
c.
d.
e.
Origin of Shikimic Acid
Starting Material
Enzymes
Pathway- Mechanism
Product
2. Aromatic Amino Acids
a.
b.
c.
d.
e.
What are the Aromatic Amino Acids
Starting Material
Enzymes
Pathway- Mechanism
Products
3. Phenolic Compounds
a.
b.
c.
d.
e.
What are Phenolic Compounds
Starting Material
Enzymes
Pathway- Mechanism
Products
DEFINITION OF TERMS
1. Shikimic acid or shikimate: is an important
biochemical metabolite in plants and
microorganisms.
2. Aromatic compound: is a hydrocarbon with
alternating double bonds and single bonds
between carbon atoms
3. Amino acids: are molecules containing an
amine group, a carboxylic acid group and a side
chain (specific)
4. Phenolic Compounds: are a large and diverse
group of molecules, which includes many
families of aromatic secondary metabolite in
plants.
5. Enzymes: are group of molecules that serve as
a catalyst with a high degree of specificity for
a certain substrate or class of substrates. It can
only act on one substrate or on a family of
structurally similar substrates.
MAJOR ENZYMES
1. Synthase: Joints two molecules together w/o
hydrolyzing a pyrophosphate bond.
2. Dehydratase: Removes water to create a
double bond
3. Dehydrogenase: Removes hydrogen atom from
its substrate
4. Kinase: Transfer a phosphate group from a
high-energy phosphate compound such as ATP
to its substrate.
SHIKIMIC ACID
Where this came from?
Shikimi
Illicium anisatum
Shikimic acid is a precursor for:
1. Aromatic amino acids phenylalanine
and tyrosine
2. Indole, and indole derivatives and
a.a.a tryptophan
3. Alkaloids
4. Phenylpropanoids, flavonoids,
tannins, and lignins.
FORMATION OF SHIKIMIC ACID
Starting materials
1st: Pyruvate to Phospoenolpyruvate
FORMATION OF SHIKIMIC ACID
2nd : Erthryrose-4-phosphate
FORMATION OF SHIKIMIC ACID
Analyze this reaction, what are the other
materials involve?
FORMATION OF SHIKIMIC ACID
3-deoxy-D-arabinoheptulosonate 7phosphate (DAHP) synthase is the first
enzyme in a series of metabolic reactions
known as the shikimate pathway.
Since it is the first enzyme in the shikimate
pathway, it controls the amount of carbon
entering the pathway.
FORMATION OF SHIKIMIC ACID
FORMATION OF SHIKIMIC ACID
phosphoenol pyruvate
H
H
COOH
O
O
HO P
O C
H
PO CH2
HO
HO P
O
HO
H
O
H+
H
CH2
B:
CH2
O
HO
O C
COOH
H
CH2 HO
O
OH
H
O
H
erythrose-4-phosphate
H+
COOH
HO
COOH
H+
O C
COOH
CH2
H
NADPH
H2C
HO
OH
OH
shikimic acid
COOH
O
OH
OH
O
H
OH
OH
OH
H
O
HO
H
FORMATION OF SHIKIMIC ACID
3-dehydroquinate synthase is the second
enzyme of the shikimate pathway.
It catalyzes the elimination of phosphate
from DAHP to generate 3-dehydroquinate
(DHQ).
FORMATION OF SHIKIMIC ACID
FORMATION OF SHIKIMIC ACID
3-Dehydroquinate Dehydratase (DHQD)
catalyzes the third step of the shikimate
pathway, dehydration of 3-dehydroquinate
to 3-dehydroshikimate.
FORMATION OF SHIKIMIC ACID
FORMATION OF SHIKIMIC ACID
Shikimate-5-Dehydrogenase (SDH) The
fourth step of the shikimate pathway is the
reduction of DHS to shikimate. the reaction
is catalyzed by an NADP-dependent
shikimate dehydrogenase (SHD)
FORMATION OF SHIKIMIC ACID
FORMATION OF SHIKIMIC ACID
FORMATION OF SHIKIMIC ACID
Shikimate Kinase (SK)- In the fifth step of
the shikimate pathway, shikimate kinase
catalyzes the specific phosphorylation of the
3-hydroxyl group of D-shikimate to yield
shikimate 3-phosphate using ATP as a cosubtrate
FORMATION OF SHIKIMIC ACID
FORMATION OF SHIKIMIC ACID
5-Enolpyruvylshikimate 3-Phosphate
Synthase (EPSPS) is the sixth enzyme of the
shikimate pathway. It catalyzes the reversible
formation of 5-enolpyruvyl-shikimate-3phosphate (EPSP) from shikimate 3phosphate and PEP.
FORMATION OF SHIKIMIC ACID
FORMATION OF SHIKIMIC ACID
Chorismate Synthase (CS) The seventh and
final step in the main trunk of the shikimate
pathway is the trans-1,4 elimination of
phosphate from EPSP to yield chorismate
FORMATION OF SHIKIMIC ACID
In this reaction, the second of the three
double bonds of the benzene ring is
introduced. The reaction is catalyzed by
chorismate synthase and requires reduced
flavin for activity even though the overall
reaction is redox neutral.
FORMATION OF SHIKIMIC ACID
SHIKIMIC ACID TO AROMATIC ACID
The seven-step shikimate pathway links
the metabolism of carbohydrates to the
biosynthesis of aromatic amino acids and
many aromatic secondary metabolites,
including tetrahydrofolate and
ubiquinone.
Aromatic Amino
Acids
Aromatic Amino Acids
1. What are aromatic amino acids?
Aromatic Amino Acids are amino acids that
include an aromatic ring.
Example includes:
Phenylalanine, Tryptophan, Histidine,
Tyrosine
(but only F, W, Y can be synthesized by
Shikimate pathway)
The Aromatic Family
In plants and microorganism:
Phe, Tyr, and Trp
 Precursors are:
 PEP
 ERYTHROSE-4-PHOSPHATE
 CHORISMATE
The Starting Material
CHORISMATE
Enzymes
Isomerase is an enzyme that catalyzes the
structural rearrangement of isomers.
Mutase: catalyzes the shifting of a
functional group from one position to
another within the same molecule.
Transferase: catalyzes the transfer of
a functional group (methyl or
phosphate)from one molecule to another
The Pathway
The Mechanisms
From Chorismate to Prephenate
The Mechanisms
What is Claisen Rearrangement?
Claisen Rearrangement is a
powerful carbon-carbon bondforming chemical reaction discovered
by Rainer Ludwig Claisen.
In NMR spectrum (chair conformation)
-O
2C
O
OH
13.6
COO-
Chair and Boat Conformation
-OOC
H
3H
-OOC
O
COO-
A
COO-
chair
OH
13.8
Z-13.7
O
B
3H
O
OH
3H
pro-S
H
pro-R
H
COOCOO-
3H
COO-
H
O
COO-
boat
OH
OH
Z-13.7
13.9
OVER-ALL STRUCTURE
7
9
COO1
6
4
HO
CH2 C
-OOC
9
2
CH2
3
5
O
O 8
COO-
7
13.1
CHORISMATE
1
6
5
8
COO-
2
3
4
HO
13.2
PREPHENATE
Phenylalanine Biosynthesis
Prephenate dehyrdatase to Phenylpyruvate
The Mechanism
Phenylpyruvate to Phenylalanine
Phenylalanine aminotransferase catalyze this
reaction
The Mechanisms
Prephenate to Phenylpyurvate to Phenylalanine
SOURCES OF ESSENTIAL AMINO ACIDS
Phenylalanine
Tyrosine Biosynthesis
The Mechanism
Prephenate to p-Hydroxyphenylpyruvate
Prephenate dehydrogenase catalyzed this reaction.
The Mechanism
p-Hydroxyphenylpyruvate to Tyrosine
Tyrosine aminotransferase catalyzed this reaction
SOURCES OF ESSENTIAL AMINO ACIDS
Tyrosine
OVER-ALL PATHWAY
Tryptophan Biosynthesis
The Mechanism
This reaction
is catalyzed by
athranilate
synthase
The Mechanism
This reaction is
catalyzed by
athranilate
phosphoribosyl
transferase
The Mechanism
This reaction is
catalyzed by
phosphoribosyl
athranilate
isomerase.
The Mechanism
This reaction is
catalyzed by
indole-3glucerol
phosphate
synthase.
This reaction is
catalyzed by
tryptrophan
synthase
OVER-ALL PATHWAY
SOURCES OF ESSENTIAL AMINO ACIDS
Tryptophan
SOURCES OF ESSENTIAL AMINO ACIDS
Phenylalanine
SOURCES OF ESSENTIAL AMINO ACIDS
Tyrosine
SOURCES OF ESSENTIAL AMINO ACIDS
Tryptophan
AMINO ACID DEGRADATION INTERMEDIATES
Glucogenic
Ala
Cys
Gly
Ketogenic
* Both Glucogenic and Ketogenic
• Purely Ketogenic
CO2
Glucose
Ile*
Leu•
Lys•
Thr*
Ser
Thr*
Trp*
Pyruvate
Acetyl-CoA
Acetoacetate
Asn
Asp
Citrate
Oxaloacetate
Asp
Phe*
Tyr*
Fumarate
Leu•
Lys•
Phe*
Citric
Acid
Cycle
Trp*
Tyr*
Isocitrate
CO2
Ile*
Met
Val
Succinyl-CoA
a-ketoglutarate
CO2
Arg
Glu
Gln
His
Pro
PHENOLICS
These are the class of natural occuring compound
with one or more phenolic compounds or
benzene ring with –OH group.
Quercetin, a typical flavonoid, is
a natural phenol
BIOSYNTHESIS OF PHENOLICS
Most of the natural phenols
are derived from secondary
plant metabolism of the
shikimic acid pathway, malic
acid pathway or both.
APPLICATIONS
One very good example
are HORSE GRAMS- a kind
of beans
SOURCES OF PHENOLIC ACIDS
Horse Grams/ beans has the following kinds of
phenolic acids:
Caffeic Acid
Protocatechuic
acid
p-coumaric acid
Thank You
for
Listening!