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SHIKIMIC ACID PATHWAY
HANDOUTHANDOUT--KBAKBA--20102010
THE SHIKIMIC ACID PATHWAYTHE SHIKIMIC ACID PATHWAY
This pathway (unique to plants) leads to the
formation of the
aromatic amino acids phenylalanine and
tyrosine and to the
formation of many other phenyl-C3
compounds.
Cleavage of the C3 side chain leads to many
phenyl-C1 compounds.
C C C
PhenylpropanoidsPhenylpropanoids
Phenyl-C3
CC C C
Phenyl-C1
glycolysis
PEP
GLUCOSE
Acetyl-CoA
pentose
phosphate
pathway
Erythrose-4-phosphate
Phosphoenol pyruvate
Shikimic Acid
ORIGINS OF THEORIGINS OF THE
SHIKIMIC ACIDSHIKIMIC ACID
PATHWAYPATHWAY
The pentose phosphate
pathway is one that
converts glucose into
sugars of different sizes
(different numbers of C)
by acyl interchanges.
Erythrose is a 4-carbon
sugar.
OH P
O
O
O C
CH2
COOH
O
OH HCH2
OH
H
H
PO
H+
H
OH
erythrose-4-phosphate
phosphoenol pyruvate
O C
CH2
COOH
OH
OH H
OHH
H
CH2
OP
O
O
OH
O C
CH2
COOH
OH
OH H
CH2
H
OH
H+
O
OH
OH
H
OHCOOH
O
OH
OH
COOH
OH
OH
OH
COOH
shikimic acid
NADPH
H+
FORMATION OF SHIKIMIC ACIDFORMATION OF SHIKIMIC ACID
B:
FORMATION OF CHORISMIC ACIDFORMATION OF CHORISMIC ACID
OH
OH
OH
COOH
shikimic acid
ATP
O
OH
OH
COOH
P
C O
CH3
COOH
pyruvic acid
H+
hydrolysis
of PEP
O
OH
O
COO H
P C
CH3
COOH
OHO
OH
O
COOH
P C
CH2
COOH
H
OH
O
COOH
C
CH2
COOH
chorismic acid
:B- H2O
nucleophilic
addition to C=O
- H3PO4
PREPHENIC ACIDPREPHENIC ACID
OC
CH2
COOH
C
O
OHH
OH
chorismic acid
Claisen Type
Rearrangement
OH
H
CH2
C
O
HOOC
C
O
O H
prephenic acid
H OH
CH2
HOOC C
O
COOH
phenypyruvic
acid
p-hydroxy-phenylpyruvic
acid
NADP+NADPH
- CO2-H+ -H-
Prephenic acid can be converted to
phenylpyruvic acid
or to 4-hydroxyphenylpyruvic acid:
tyrosine phenylalanine
- CO2-H+ -OH
pseudoaxial conformation
CLAISEN REARRANGEMENTCLAISEN REARRANGEMENT
O
CHR
an allyl ether
heatO
CHRH
OH
CHR
an allyl phenol
enolization
H+
A THERMAL REARRANGEMENT
PREPHENIC ACID TO PHENYLALANINEPREPHENIC ACID TO PHENYLALANINE
OH
H
CH2
C
O
HOOC
C
O
O H
prephenic acid
:B-Enz
H+
CH2
C
O
COOH
transamination
phenylpyruvic acid
CH2
CH CO O H
NH2
phenylalanine
- CO2
- H2O
PREPHENIC ACID TO TYROSINEPREPHENIC ACID TO TYROSINE
OH
H
CH2
C
O
HOOC
C
O
O H
prephenic acid
:B-Enz
NAD+
CH2
C
O
COOH
OH
transamination
4-hydroxyphenyl-
pyruvic acid
CH2
CH COOH
OH
NH2
tyrosine
hydride transfer
to NAD+
- CO2
CH2
CH COOH
OH
NH2
tyrosine
CH2
CH CO OH
NH2
phenylalanine
PREPHENIC ACIDPREPHENIC ACID
phenylpyruvicphenylpyruvic acidacid 44--hydroxyphenylpyruvic acidhydroxyphenylpyruvic acid
X
PHENYLALANINE AND TYROSINE COME FROM PHENYLALANINE AND TYROSINE COME FROM
A COMMON SOURCE AND ARE NOT CONVERTEDA COMMON SOURCE AND ARE NOT CONVERTED
Although most plants could convert phenylalanine to tyrosine
using hydroxylases, this conversion is a minor pathway. Most
plants make enough tyrosine without converting phenylalanine.
A PRELIMINARY OVERVIEW
CHORISMIC ACID
SHIKIMIC ACID
PREPHENIC
ACID
TYROSINE
PHENYLALANINE
CINNAMIC
ACIDS
ALKALOIDS ALKALOIDS
PHENYL-C3
COMPOUNDS
Shikimate
Pathways
PHENYL-C1
COMPOUNDS
FLAVONOIDS
(+ acetogenin piece)
CINNAMYL COMPOUNDSCINNAMYL COMPOUNDS
CINNAMYL COMPOUNDSCINNAMYL COMPOUNDSCH
2C
O
COOH
CH2
C
OH
COOH
H
CH CH COOH
NADPH
- H2O
CH CH C S-Enz
O
CH CH C H
O
C
O
H
oxidative
cleavage
Enz-SH
NADPH
cinnamic acid
cinnamaldehyde
benzaldehyde
The rings can have various numbers of hydroxyl
or methoxyl groups (hydroxylases and SAM).
CH2
CH2
COOH
hydrocinnamic acid
FADH2
COOH COOH
OH
COOH
OH
OH
COOH
OH
OMe
COOH
OH
OMeOH
p-coumaric acid caffeic acid ferulic acid
sinapic acid
COOH
OH
OMeMeO
CH2OH
OH
CH2OH
OH
OMe
CH2OH
OH
OMeMeO
p-coumarylalcohol
coniferyl
alcohol
sinapyl
alcohol
SOME NATURALLYSOME NATURALLY--OCCURING CINNAMYL COMPOUNDSOCCURING CINNAMYL COMPOUNDS
CINNAMIC
ACID
corresponding
aldehydes are
also found -
see next slide
sinapic acid
COOH
OH
OMeMeO
C
OH
OMeMeO
O
SCoA C
OH
OMeMeO
O
HCH
2
OH
OMeMeO
OH
HSCoA NADPH NADPH
sinapyl alcoholsinapyl aldehyde
TYPICAL REDUCTION SEQUENCESTYPICAL REDUCTION SEQUENCES
COOH
OMe OMe
CH2OH
OMe
OMe
anethole
estragole
(methylchavicol)
CLEAVAGE TO CLEAVAGE TO
PHENYLPHENYL--C1 COMPOUNDSC1 COMPOUNDS
CLEAVAGE TO PHENYLCLEAVAGE TO PHENYL--C1 COMPOUNDSC1 COMPOUNDS
COOH
OH
MeO
OH
MeO
C SCoA
O
OH
MeO
C SCoA
O
OH
CCH
2
OH
MeO
C SCoA
O
O
C
OH
MeO
OSCoA
S
H
CoA:
C
OH
MeO
OOH
vanillic acid
CH2
COOH
OH
MeO
O
H
H
C
OH
MeO
OH
vanillin
reverse
aldol
reverse
Claisen
H2O
H2O
H2O
ferulic acid
HSCoA NADP+
COUMARINSCOUMARINS
COOH C OOH
O H OHCOOH
O OO OOH
umbelliferone
O OOH
OH
aesculetin
FORMATION OF COUMARINSFORMATION OF COUMARINS
isomerization
lactone
(ester)
hydroxylase
coumarin
DICOUMAROL AND WARFARINDICOUMAROL AND WARFARIN
O O OO
OH OH
dicoumarol(sweet clover)
O
O
O
OH
Warfarin
O O
O
OO
OH
O O
OH
HC
H
O
OH
C
O
SCoA
OH
C C
O
SCoA
O
..
:
- H2O
cinnamic acid
anti-coagulant
RODENTICIDE(rat poison)
causes internal
bleeding in cows
FLAVONOIDSFLAVONOIDS
Plant Pigments
PLANT PIGMENTSPLANT PIGMENTS
Flavonoids and anthocyanins are conspicuous plant pigments in nature that
are responsible for the beauty and splendor of flowers, fruits, fruit tree blossoms
and of the autumn leaves.
Flavones are responsible for the yellow and orange colors; and the anthocyanins
are the source of red, violet and blue colors. These compounds occur mainly in
higher plants and are less common in the lower orders. You don’t find them in
algae, fungi or bacteria.
The flavonoids play a major role in attracting insects to feed and pollinate these
plants. Some of them also have a bitter taste and repel harmful insects like
caterpillars.
Flavonoids are thought to be antioxidants, and play a major role in our diet,
preventing the ravages of aging caused by free-radicals.
These compound have their biosynthetic origin in both the skimic acid pathway
and the acetogenin pathway - they are of hybrid origin.
NARINGENINNARINGENIN
O
CoAS
OH
malonyl-CoA
3x
OH
SCoA
OO
O
O
OH
OH O
OH
O
:
OH
OH O
OH
O
H
naringenin
A FLAVONE
internal Claisen
and enolizations
A different starter
than acetyl-CoA.
acetogenin
pathway
shikimic acid
pathway
MIXED-ORIGIN
COMPOUND
found in grapefruit
Michael
addition
flavones are yellow
or orange pigments
Anthocyanin
Flower Pigments
Anthocyanin Leaf PigmentsAutumn Leaves
In Spring and Summer
chlorophyll (green) masks
the anthocyanin colors.
OH
OH O
OH
O
R
naringenin (R=H)
OH
OH O
OH
O
OH
R
OH
OH O
OH
OH
OH
R
NADPH
[O]
OH
OH O
OH
OH
OH
R
OH
OH
OH O
OH
OH
R
+
- 2 H2O
O2
pelargonidin (R=H)
cyanidin (R=OH)
ANTHOCYANIDINS AND ANTHOCYANINSANTHOCYANIDINS AND ANTHOCYANINS
plant flower and
leaf pigmentsANTHOCYANIDINS
cyanidin is blue
pelargonidin is pink
Anthocyanins are
red, violet or blue
pigments.