HANDOUT-KBA-2010

SHIKIMIC ACID PATHWAY

 THE 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.
Phenylpropanoids
C C C Phenyl-C3

Cleavage of the C3 side chain leads to many

phenyl-C1 compounds.

C C C C

Phenyl-C1
 GLUCOSE ORIGINS OF THE
pentose
phosphate
SHIKIMIC ACID
pathway glycolysis PATHWAY

Erythrose-4-phosphate PEP
Phosphoenol pyruvate
The pentose phosphate
pathway is one that
converts glucose into
sugars of different sizes
(different numbers of C)
by acyl interchanges.
Acetyl-CoA Erythrose is a 4-carbon
sugar.
Shikimic Acid
 FORMATION OF SHIKIMIC ACID
H phosphoenol pyruvate
COOH
O O C
H O COOH
HO P O C CH2
CH2
B: H
O HO OH
H
O
H H+ H
HO O HO P O CH2 HO
H
O
PO CH2 HO H

erythrose-4-phosphate

H+ H+
COOH
HO
COOH COOH COOH O C
CH2
NADPH H
H2C H
OH
HO OH O OH O OH
OH HO H
OH OH H O

shikimic acid
 FORMATION OF CHORISMIC ACID
hydrolysis
COOH COOH
of PEP

ATP
HO OH P O OH CH3
OH OH C O
COOH H+
shikimic acid pyruvic acid

nucleophilic
addition to C=O

COOH CO O H CO O H
:B
- H3PO4 H - H2O
C H2 CH 2 CH 3
O C P O O C P O O C OH
OH COOH OH COOH OH CO O H

chorismic acid
 PREPHENIC ACID
chorismic acid
HOOC
COOH
C
Claisen Type CH2
O C CH Rearrangement
O
2 C O H
H
C OH H O

HO O
OH prephenic acid
pseudoaxial conformation

Prephenic acid can be converted to

phenylpyruvic acid
O
or to 4-hydroxyphenylpyruvic acid:
HOOC CH2 C
COOH
NADPH NADP+
p-hydroxy- phenypyruvic
phenylpyruvic -H+ - CO2 -H-
H OH
-H+ - CO2 -OH acid
acid

tyrosine phenylalanine
 CLAISEN REARRANGEMENT
A THERMAL REARRANGEMENT

CHR
CHR CHR
H
O O OH
heat H+
enolization

an allyl ether an allyl phenol

PREPHENIC ACID TO PHENYLALANINE
HOOC
C
CH2 O
O :B-Enz
C O H C H2 C CO O H

H O
- CO2
- H2O phenylpyruvic acid
OH prephenic acid

H+ transamination

C H2 C H CO O H
N H2

phenylalanine
 PREPHENIC ACID TO TYROSINE
HOOC
C
O CH2 :B-Enz O
C O H C H2 C COOH

H O
- CO2 HO
NAD+ 4-hydroxyphenyl-
OH prephenic acid pyruvic acid

transamination
hydride transfer
to NAD+

CH 2 C H CO O H
N H2
HO
tyrosine
PHENYLALANINE AND TYROSINE COME FROM
A COMMON SOURCE AND ARE NOT CONVERTED

PREPHENIC ACID

phenylpyruvic acid 4-hydroxyphenylpyruvic acid

CH2 C H CO O H CH2 CH CO O H
N H2 X N H2
HO

phenylalanine tyrosine

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
Shikimate SHIKIMIC ACID
Pathways
CHORISMIC ACID
(+ acetogenin piece)

PREPHENIC PHENYL-C3
FLAVONOIDS
ACID COMPOUNDS

TYROSINE CINNAMIC
ACIDS
PHENYLALANINE
PHENYL-C1
COMPOUNDS

ALKALOIDS ALKALOIDS
CINNAMYL COMPOUNDS
 O CINNAMYL COMPOUNDS
C H2 C COOH The rings can have various numbers of hydroxyl
or methoxyl groups (hydroxylases and SAM).
NADPH
O
OH CH CH C H
C H2 C COOH
cinnamaldehyde
H
NADPH
- H2O
O
Enz-SH
CH CH CO OH CH CH C S-E nz

oxidative
FADH2 cleavage
cinnamic acid
O
C
C H2 C H 2 C O O H H

benzaldehyde
hydrocinnamic acid
SOME NATURALLY-OCCURING CINNAMYL COMPOUNDS

COOH COOH COOH COOH COOH

OH OMe HO OMe
OH OH OH OH
CINNAMIC
ACID
p-coumaric acid caffeic acid ferulic acid

CH2OH CH2OH CH2OH COOH

corresponding
aldehydes are
also found -
see next slide MeO MeO
OMe OMe OMe
OH OH OH OH

p-coumaryl coniferyl sinapyl sinapic acid

alcohol alcohol alcohol
 TYPICAL REDUCTION SEQUENCES
O O
COOH CH 2 OH
C SCoA C H

HSCoA NADPH NADPH

MeO OMe M eO OMe

MeO OMe MeO OMe
OH OH
OH OH
sinapic acid sinapyl aldehyde sinapyl alcohol

COOH CH2OH

estragole
OMe
(methylchavicol)

OMe OMe

OMe anethole
 CLEAVAGE TO
PHENYL-C1 COMPOUNDS
 CLEAVAGE TO PHENYL-C1 COMPOUNDS
O O O
COOH C SCoA C SCoA C SCoA
HO O CH2
HSCoA H2O NADP+ C

:S CoA

MeO H
MeO MeO MeO
OH OH OH OH
ferulic acid
reverse
Claisen
H2O
O O
C OH C SCoA
H COOH H2O
CH2 O
O C H
H
MeO M eO
OH OH
reverse MeO
MeO aldol vanillic acid
OH
OH

vanillin
COUMARINS
 FORMATION OF COUMARINS

COOH C OOH

COOH
OH OH
hydroxylase isomerization
lactone
(ester)

HO O O O O

umbelliferone coumarin

HO

HO O O

aesculetin
 DICOUMAROL AND WARFARIN
H
O O O :O O
C C C H C H
SCoA SCoA

OH
..OH O O

- H2O
O OH

cinnamic acid
O O O O

RODENTICIDE
(rat poison)
OH OH

OH O

O O O O

O O
causes internal dicoumarol
bleeding in cows (sweet clover)
Warfarin
anti-coagulant
FLAVONOIDS

Plant Pigments
 PLANT 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.
shikimic acid
pathway OH
NARINGENIN
C oAS A different starter found in grapefruit
O
than acetyl-CoA.

malonyl-CoA acetogenin
3x pathway

OH OH
O S CoA H
HO O :
O

O O OH O Michael
internal Claisen addition
and enolizations
OH

HO O
MIXED-ORIGIN A FLAVONE
COMPOUND
flavones are yellow OH O
or orange pigments
naringenin
Anthocyanin
Flower Pigments
Anthocyanin Leaf Pigments
Autumn Leaves

In Spring and Summer

chlorophyll (green) masks
the anthocyanin colors.
 ANTHOCYANIDINS AND ANTHOCYANINS
OH OH OH

HO O HO O HO O
R R R

OH NADPH OH
O2
OH O OH O OH OH

naringenin (R=H)

[O]

OH OH
+ OH
HO O HO O
R R

OH OH
Anthocyanins are - 2 H2O
OH OH OH
red, violet or blue
pigments. pelargonidin (R=H)
cyanidin (R=OH)
plant flower and cyanidin is blue
ANTHOCYANIDINS pelargonidin is pink
leaf pigments