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 Phenyl-C3 Cleavage of the C3 side chain leads to many phenyl-C1 compounds. Phenyl-C1

GLUCOSE ORIGINS OF THE SHIKIMIC ACID PATHWAY PEP Acetyl-CoA pentose phosphate pathway glycolysis 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. Erythrose is a 4-carbon sugar. Acetyl-CoA Shikimic Acid

FORMATION OF SHIKIMIC ACID phosphoenol pyruvate B: H+ erythrose-4-phosphate H+ H+ NADPH shikimic acid

FORMATION OF CHORISMIC ACID hydrolysis of PEP ATP H+ shikimic acid pyruvic acid nucleophilic addition to C=O :B - H3PO4 - H2O chorismic acid

PREPHENIC ACID phenylalanine tyrosine p-hydroxy- phenypyruvic chorismic acid Claisen Type Rearrangement prephenic acid pseudoaxial conformation Prephenic acid can be converted to phenylpyruvic acid or to 4-hydroxyphenylpyruvic acid: NADPH NADP+ p-hydroxy- phenylpyruvic acid phenypyruvic acid -H+ - CO2 -H- -H+ - CO2 -OH phenylalanine tyrosine

CLAISEN REARRANGEMENT A THERMAL REARRANGEMENT H+ heat enolization an allyl ether an allyl phenol

PREPHENIC ACID TO PHENYLALANINE :B-Enz - CO2 phenylpyruvic acid - H2O prephenic acid H+ transamination phenylalanine

PREPHENIC ACID TO TYROSINE :B-Enz - CO2 4-hydroxyphenyl- pyruvic acid NAD+ prephenic acid transamination hydride transfer to NAD+ tyrosine

PHENYLALANINE AND TYROSINE COME FROM A COMMON SOURCE AND ARE NOT CONVERTED PREPHENIC ACID phenylpyruvic acid 4-hydroxyphenylpyruvic acid X tyrosine phenylalanine 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 Pathways SHIKIMIC ACID CHORISMIC ACID PREPHENIC ACID (+ acetogenin piece) PREPHENIC ACID PHENYL-C3 COMPOUNDS FLAVONOIDS CINNAMIC ACIDS TYROSINE PHENYLALANINE PHENYL-C1 COMPOUNDS ALKALOIDS ALKALOIDS

CINNAMYL COMPOUNDS

CINNAMYL COMPOUNDS The rings can have various numbers of hydroxyl or methoxyl groups (hydroxylases and SAM). NADPH cinnamaldehyde NADPH - H2O Enz-SH oxidative cleavage FADH2 cinnamic acid benzaldehyde hydrocinnamic acid

SOME NATURALLY-OCCURING CINNAMYL COMPOUNDS CINNAMIC ACID p-coumaric acid caffeic acid ferulic acid corresponding aldehydes are also found - see next slide p-coumaryl alcohol coniferyl alcohol sinapyl alcohol sinapic acid

TYPICAL REDUCTION SEQUENCES HSCoA NADPH NADPH sinapic acid sinapyl aldehyde sinapyl alcohol estragole (methylchavicol) anethole

CLEAVAGE TO PHENYL-C1 COMPOUNDS

CLEAVAGE TO PHENYL-C1 COMPOUNDS HSCoA H2O NADP+ : ferulic acid reverse Claisen H2O H2O reverse aldol vanillic acid vanillin

COUMARINS

FORMATION OF COUMARINS hydroxylase isomerization lactone (ester) umbelliferone coumarin aesculetin

DICOUMAROL AND WARFARIN : .. - H2O cinnamic acid RODENTICIDE (rat poison) dicoumarol causes internal 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.

NARINGENIN found in grapefruit : MIXED-ORIGIN COMPOUND shikimic acid pathway NARINGENIN A different starter than acetyl-CoA. found in grapefruit malonyl-CoA 3x acetogenin pathway : Michael addition internal Claisen and enolizations MIXED-ORIGIN COMPOUND A FLAVONE flavones are yellow 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 NADPH naringenin (R=H) [O] + Anthocyanins are red, violet or blue pigments. - 2 H2O pelargonidin (R=H) cyanidin (R=OH) plant flower and leaf pigments cyanidin is blue pelargonidin is pink ANTHOCYANIDINS

SUMMARY REPEAT

Shikimate Pathways SHIKIMIC ACID FLAVONOIDS CHORISMIC ACID PREPHENIC (+ acetogenin piece) Shikimate Pathways SHIKIMIC ACID FLAVONOIDS CHORISMIC ACID PREPHENIC ACID PHENYL-C3 COMPOUNDS ANTHRANILIC ACID CINNAMIC ACIDS TYROSINE TRYPTOPHAN PHENYLALANINE PHENYL-C1 COMPOUNDS ALKALOIDS ALKALOIDS ALKALOIDS