SHIKIMIC ACID PATHWAY

THE SHIKIMIC ACID PATHWAYTHE SHIKIMIC ACID PATHWAYThis 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 PhenylpropanoidsPhenylpropanoidsPhenyl-C3

CC C C

Phenyl-C1

glycolysis

PEP

GLUCOSE

Acetyl-CoA

pentose phosphatepathway

Erythrose-4-phosphatePhosphoenol pyruvate

Shikimic Acid

ORIGINS OF THEORIGINS OF THESHIKIMIC ACIDSHIKIMIC ACIDPATHWAYPATHWAY

The pentose phosphatepathway is one that converts glucose intosugars of different sizes(different numbers of C)by acyl interchanges.Erythrose is a 4-carbonsugar.

OH PO

OO C

CH2

COOH

O

OH HCH2

OHH

H

PO

H+

HO

H

erythrose-4-phosphate

phosphoenol pyruvate

O CCH2

COOH

OH

OH H

OHH

H

CH2OP

O

O

OH

O CCH2

COOH

OH

OH H

CH2 H

OH

H+

OOH

OH

H

OHCOOH

OOH

OH

COOH

OHOH

OH

COOH

shikimic acid

NADPH

H+

FORMATION OF SHIKIMIC ACIDFORMATION OF SHIKIMIC ACID

B:

FORMATION OF CHORISMIC ACIDFORMATION OF CHORISMIC ACID

OHOH

OH

COOH

shikimic acid

ATPO

OHOH

COOH

PC OCH3

COOHpyruvic acid

H+

hydrolysisof PEP

OOH

O

COOH

P CCH3

COOHOHO

OHO

COOH

P C

CH2

COOH

H

OHO

COOH

C

CH2

COOH

chorismic acid

:B- H2O

nucleophilicaddition to C=O

- H3PO4

PREPHENIC ACIDPREPHENIC ACID

O CCH2

COOH

CO

OHH

OH

chorismic acid

Claisen TypeRearrangement

OH

H

CH2C

O

HOOC

CO

O H

prephenic acid

H OH

CH2HOOC CO

COOH

phenypyruvic acid

p-hydroxy-phenylpyruvicacid

NADP+NADPH

- CO2-H+ -H-

Prephenic acid can be converted to phenylpyruvic acidor to 4-hydroxyphenylpyruvic acid:

tyrosine phenylalanine

- CO2-H+ -OH

pseudoaxial conformation

CLAISEN REARRANGEMENTCLAISEN REARRANGEMENT

OCHR

an allyl ether

heat OCHRH

OHCHR

an allyl phenol

enolization

H+

A THERMAL REARRANGEMENT

PREPHENIC ACID TO PHENYLALANINEPREPHENIC ACID TO PHENYLALANINE

OH

H

CH2C

O

HOOC

CO

O H

prephenic acid

:B-Enz

H+

CH2 CO

COOH

transamination

phenylpyruvic acid

CH2 CH COOHNH2

phenylalanine

- CO2- H2O

PREPHENIC ACID TO TYROSINEPREPHENIC ACID TO TYROSINE

OH

H

CH2C

O

HOOC

CO

O H

prephenic acid

:B-Enz

NAD+

CH2 CO

COOH

OH

transamination

4-hydroxyphenyl- pyruvic acid

CH2 CH COOH

OHNH2

tyrosine

hydride transferto NAD+

- CO2

CH2 CH COOH

OHNH2

tyrosine

CH2 CH COOHNH2

phenylalanine

PREPHENIC ACIDPREPHENIC ACID

phenylpyruvic acidphenylpyruvic acid 4-hydroxyphenylpyruvic acid4-hydroxyphenylpyruvic 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 tyrosineusing hydroxylases, this conversion is a minor pathway. Mostplants make enough tyrosine without converting phenylalanine.

A PRELIMINARY OVERVIEW

CHORISMIC ACID

SHIKIMIC ACID

PREPHENIC ACID

TYROSINE

PHENYLALANINE

CINNAMIC ACIDS

ALKALOIDS ALKALOIDS

PHENYL-C3COMPOUNDS

ShikimatePathways

PHENYL-C1COMPOUNDS

FLAVONOIDS

(+ acetogenin piece)

CINNAMYL COMPOUNDSCINNAMYL COMPOUNDS

CINNAMYL COMPOUNDSCINNAMYL COMPOUNDSCH2 C

OCOOH

CH2 COH

COOHH

CH CH COOH

NADPH

- H2O

CH CH C S-Enz

O

CH CH C H

O

CO

H

oxidativecleavage

Enz-SH

NADPH

cinnamic acid

cinnamaldehyde

benzaldehyde

The rings can have various numbers of hydroxylor methoxyl groups (hydroxylases and SAM).

CH2 CH2 COOH

hydrocinnamic acid

FADH2

COOH COOH

OH

COOH

OHOH

COOH

OHOMe

COOH

OHOMeOH

p-coumaric acid caffeic acid ferulic acid

sinapic acid

COOH

OHOMeMeO

CH2OH

OH

CH2OH

OHOMe

CH2OH

OHOMeMeO

p-coumaryl alcohol

coniferyl alcohol

sinapylalcohol

SOME NATURALLY-OCCURING CINNAMYL COMPOUNDSSOME NATURALLY-OCCURING CINNAMYL COMPOUNDS

CINNAMICACID

correspondingaldehydes arealso found -see next slide

sinapic acid

COOH

OHOMeMeO

C

OHOMeMeO

OSCoA C

OHOMeMeO

OH CH2

OHOMeMeO

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 PHENYL-C1 COMPOUNDSPHENYL-C1 COMPOUNDS

CLEAVAGE TO PHENYL-C1 COMPOUNDSCLEAVAGE TO PHENYL-C1 COMPOUNDS

COOH

OHMeO

OHMeO

C SCoAO

OHMeO

C SCoAO

OHCCH2

OHMeO

C SCoAO

O

C

OHMeO

OSCoA

SH

CoA:

C

OHMeO

OOH

vanillic acid

CH2

COOH

OHMeO

OH

H

C

OHMeO

OH

vanillin

reversealdol

reverseClaisen

H2O

H2O

H2O

ferulic acid

HSCoA NADP+

COUMARINSCOUMARINS

COOH COOH

OH OHCOOH

O OO OOH

umbelliferone

O OOH

OH

aesculetin

FORMATION OF COUMARINSFORMATION OF COUMARINS

isomerizationlactone(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

H C H

O

OH

CO

SCoA

OH

C CO

SCoA

O

..

:

- H2O

cinnamic acid

anti-coagulant

RODENTICIDE(rat poison)

causes internalbleeding in cows

FLAVONOIDSFLAVONOIDS

Plant Pigments

PLANT PIGMENTSPLANT PIGMENTSFlavonoids and anthocyanins are conspicuous plant pigments in nature thatare 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 anthocyaninsare the source of red, violet and blue colors. These compounds occur mainly inhigher plants and are less common in the lower orders. You don’t find them inalgae, fungi or bacteria.

The flavonoids play a major role in attracting insects to feed and pollinate theseplants. 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 pathwayand the acetogenin pathway - they are of hybrid origin.

NARINGENINNARINGENINO

CoAS

OH

malonyl-CoA3x

OHSCoA

OO

O

O

OH

OH O

OH

O

:

OH

OH O

OH

O

H

naringenin

A FLAVONE

internal Claisenand enolizations

A different starterthan acetyl-CoA.

acetogeninpathway

shikimic acidpathway

MIXED-ORIGINCOMPOUND

found in grapefruit

Michaeladdition

flavones are yellowor orange pigments

AnthocyaninFlower Pigments

Anthocyanin Leaf PigmentsAutumn Leaves

In Spring and Summerchlorophyll (green) masksthe anthocyanin colors.

OH

OH O

OH

O

R

naringenin (R=H)

OH

OH O

OH

OOH

R

OH

OH O

OH

OHOH

R

NADPH

[O]

OH

OH O

OH

OHOH

R

OH

OH

OH O

OH

OH

R

+

- 2 H2O

O2

pelargonidin (R=H)cyanidin (R=OH)

ANTHOCYANIDINS AND ANTHOCYANINSANTHOCYANIDINS AND ANTHOCYANINS

plant flower andleaf pigmentsANTHOCYANIDINS cyanidin is blue

pelargonidin is pink

Anthocyanins arered, violet or bluepigments.

SUMMARYSUMMARY

REPEAT

CHORISMIC ACID

SHIKIMIC ACID

PREPHENIC ACID

TYROSINE

PHENYLALANINE

CINNAMIC ACIDS

ALKALOIDS ALKALOIDS

PHENYL-C3COMPOUNDS

ANTHRANILIC ACID

TRYPTOPHAN

ALKALOIDS

ShikimatePathways

PHENYL-C1COMPOUNDS

FLAVONOIDS(+ acetogenin piece)

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