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.