The Metabolic Pathway of Shikimic Acid Aromatic Amino Acids Phenolic Compounds

The Metabolic Pathway of

Shikimic Acid Aromatic Amino AcidsPhenolic Compounds

Jan Michael O. SantosPhilippine Normal University

College of ScienceDepartment of Physical Sciences

Outline of Discussion1. Shikimic Acid Pathway

a. Origin of Shikimic Acidb. Starting Material c. Enzymes d. Pathway- Mechanisme. Product

2. Aromatic Amino Acids

a. What are the Aromatic Amino Acidsb. Starting Materialc. Enzymes d. Pathway- Mechanisme. Products

3. Phenolic Compounds

a. What are Phenolic Compoundsb. Starting Materialc. Enzymesd. Pathway- Mechanisme. Products

DEFINITION OF TERMS1. Shikimic acid or shikimate: is an important

biochemical metabolite in plants and microorganisms.

2. Aromatic compound: is a hydrocarbon with alternating double bonds and single bonds between carbon atoms

3. Amino acids: are molecules containing an amine group, a carboxylic acid group and a side chain (specific)

4. Phenolic Compounds: are a large and diverse group of molecules, which includes many families of aromatic secondary metabolite in plants.

5. Enzymes: are group of molecules that serve as a catalyst with a high degree of specificity for a certain substrate or class of substrates. It can only act on one substrate or on a family of structurally similar substrates.

MAJOR ENZYMES

1. Synthase: Joints two molecules together w/o hydrolyzing a pyrophosphate bond.

2. Dehydratase: Removes water to create a double bond

3. Dehydrogenase: Removes hydrogen atom from its substrate

4. Kinase: Transfer a phosphate group from a high-energy phosphate compound such as ATP to its substrate.

SHIKIMIC ACID

Where this came from?

Shikimi Illicium anisatum

Shikimic acid is a precursor for:

1. Aromatic amino acids phenylalanine and tyrosine

2. Indole, and indole derivatives and a.a.a tryptophan

3. Alkaloids 4. Phenylpropanoids, flavonoids,

tannins, and lignins.

FORMATION OF SHIKIMIC ACIDStarting materials1st: Pyruvate to Phospoenolpyruvate

FORMATION OF SHIKIMIC ACID2nd : Erthryrose-4-phosphate

FORMATION OF SHIKIMIC ACID

Analyze this reaction, what are the other materials involve?


3-deoxy-D-arabinoheptulosonate 7-phosphate (DAHP) synthase is the first enzyme in a series of metabolic reactions known as the shikimate pathway.

Since it is the first enzyme in the shikimate pathway, it controls the amount of carbon entering the pathway.

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

CH2H

OH

H+

OOH

OH

H

OHCOOH

OOH

OH

COOH

OHOH

OH

COOH

shikimic acid

NADPH

H+


B:


3-dehydroquinate synthase is the second enzyme of the shikimate pathway. It catalyzes the elimination of phosphate from DAHP to generate 3-dehydroquinate (DHQ).


3-Dehydroquinate Dehydratase (DHQD) catalyzes the third step of the shikimate pathway, dehydration of 3-dehydroquinate to 3-dehydroshikimate.


Shikimate-5-Dehydrogenase (SDH) The fourth step of the shikimate pathway is the reduction of DHS to shikimate. the reaction is catalyzed by an NADP-dependent shikimate dehydrogenase (SHD)


Shikimate Kinase (SK)- In the fifth step of the shikimate pathway, shikimate kinase catalyzes the specific phosphorylation of the 3-hydroxyl group of D-shikimate to yield shikimate 3-phosphate using ATP as a co-subtrate


5-Enolpyruvylshikimate 3-Phosphate Synthase (EPSPS) is the sixth enzyme of the shikimate pathway. It catalyzes the reversible formation of 5-enolpyruvyl-shikimate-3- phosphate (EPSP) from shikimate 3-phosphate and PEP.


Chorismate Synthase (CS) The seventh and final step in the main trunk of the shikimate pathway is the trans-1,4 elimination of phosphate from EPSP to yield chorismate


In this reaction, the second of the three double bonds of the benzene ring is introduced. The reaction is catalyzed by chorismate synthase and requires reduced flavin for activity even though the overall reaction is redox neutral.

SHIKIMIC ACID TO AROMATIC ACID

The seven-step shikimate pathway links the metabolism of carbohydrates to the biosynthesis of aromatic amino acids and many aromatic secondary metabolites, including tetrahydrofolate and ubiquinone.

Aromatic Amino Acids

F

Y

W

Aromatic Amino Acids 1. What are aromatic amino acids?

Aromatic Amino Acids are amino acids that include an aromatic ring.Example includes:Phenylalanine, Tryptophan, Histidine, Tyrosine (but only F, W, Y can be synthesized by Shikimate pathway)

The Aromatic Family

In plants and microorganism:Phe, Tyr, and Trp

Precursors are: PEP ERYTHROSE-4-PHOSPHATE CHORISMATE

The Starting Material

CHORISMATE

EnzymesIsomerase is an enzyme that catalyzes the structural rearrangement of isomers.Mutase: catalyzes the shifting of a functional group from one position to another within the same molecule.

Transferase: catalyzes the transfer of a functional group (methyl or phosphate)from one molecule to another

The Pathway

The MechanismsFrom Chorismate to Prephenate

Chorismate mutase catalyzes the Claisen rearrangement of chorismate ion

to prephenate ion

The Mechanisms

What is Claisen Rearrangement?

Claisen Rearrangement is a powerful carbon-carbon bond-forming chemical reaction discovered by Rainer Ludwig Claisen.

In NMR spectrum (chair conformation)

O

-O2C

OH

COO-

13.6

Chair and Boat Conformation

O COO-3H H

OH

COO-

O

-OOCH

3H

OH

COO-

OH

O

COO-

COO-H3H

OH

3HH

COO-O

-OOC

Z-13.7

pro-S

chair

pro-R

boat

Z-13.7

13.8

13.9

A

B

OVER-ALL STRUCTURE

COO-

HO

O COO-

CH2

HO

-OOC CH2 C

O

COO-

13.213.1

12

3

45

6

78

9 12

34

5

6

7

8

9

CHORISMATE PREPHENATE

Phenylalanine Biosynthesis

Prephenate dehyrdatase to Phenylpyruvate

The Mechanism

Phenylpyruvate to Phenylalanine

Phenylalanine aminotransferase catalyze this reaction

The Mechanisms

Prephenate to Phenylpyurvate to Phenylalanine

SOURCES OF ESSENTIAL AMINO ACIDS

Phenylalanine

Tyrosine Biosynthesis

The Mechanism

Prephenate to p-Hydroxyphenylpyruvate

Prephenate dehydrogenase catalyzed this reaction.

The Mechanism

p-Hydroxyphenylpyruvate to Tyrosine

Tyrosine aminotransferase catalyzed this reaction

SOURCES OF ESSENTIAL AMINO ACIDSTyrosine

OVER-ALL PATHWAY

Tryptophan Biosynthesis

The Mechanism

This reaction is catalyzed by

athranilate synthase

The Mechanism

This reaction is catalyzed by athranilate

phosphoribosyl transferase

The Mechanism


phosphoribosyl athranilate isomerase.

The Mechanism


indole-3-glucerol

phosphate synthase.

This reaction is catalyzed by tryptrophan

synthase

OVER-ALL PATHWAY


Tryptophan


Phenylalanine

SOURCES OF ESSENTIAL AMINO ACIDSTyrosine


Tryptophan

AMINO ACID DEGRADATION INTERMEDIATES

CO2

CO2

Pyruvate

Acetyl-CoA Acetoacetate

Citrate

Isocitrate

a-ketoglutarateSuccinyl-CoA

Fumarate

Oxaloacetate

CitricAcid

Cycle

CO2

Glucose

Ala SerCys Thr*Gly Trp*

Ile*Leu•

Lys•

Thr*

Leu• Trp*Lys• Tyr*Phe*

AsnAsp

AspPhe*Tyr*

Ile*MetVal

Arg HisGlu ProGln

Glucogenic

Ketogenic

* Both Glucogenic and Ketogenic• Purely Ketogenic

PHENOLIC ACID

PHENOLICSThese are the class of natural occuring compound with one or more phenolic compounds or benzene ring with –OH group.

Quercetin, a typical flavonoid, is a natural phenol

BIOSYNTHESIS OF PHENOLICS

Most of the natural phenols are derived from secondary plant metabolism of the shikimic acid pathway, malic acid pathway or both.

APPLICATIONS

One very good example are HORSE GRAMS- a kind

of beans

SOURCES OF PHENOLIC ACIDSHorse Grams/ beans has the following kinds of phenolic acids:

Protocatechuic acidCaffeic Acid p-coumaric acid

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The Metabolic Pathway of Shikimic Acid Aromatic Amino Acids Phenolic Compounds

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