The shikimate pathway (

shikimic acid Shikimic acid, more commonly known as its anionic form shikimate, is a cyclohexene, a cyclitol and a cyclohexanecarboxylic acid. It is an important biochemical metabolite in plants and microorganisms. Its name comes from the Japanese flower ''shik ...

pathway) is a seven-step

metabolic pathway In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell. The reactants, products, and intermediates of an enzymatic reaction are known as metabolites, which are modified by a sequence of chemical reac ...

used by

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typically a few micrometr ...

, archaea,

fungi A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...

alga Algae (; singular alga ) is an informal term for a large and diverse group of photosynthetic eukaryotic organisms. It is a polyphyletic grouping that includes species from multiple distinct clades. Included organisms range from unicellular mic ...

e, some

protozoans Protozoa (singular: protozoan or protozoon; alternative plural: protozoans) are a group of single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microorganisms or organic tissues and debris. Histo ...

, and

plant Plants are predominantly photosynthetic eukaryotes of the kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all current definitions of Plantae exclu ...

s for the biosynthesis of

folate Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing an ...

s and

aromatic amino acid An aromatic amino acid is an amino acid that includes an aromatic ring. Among the 20 standard amino acids, the following are classically considered aromatic: phenylalanine, tryptophan and tyrosine. Although histidine contains an aromatic ring, ...

s (

tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromatic ...

, phenylalanine, and

tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the G ...

). This pathway is not found in animal cells. The seven enzymes involved in the shikimate pathway are

DAHP synthase 3-Deoxy-D-arabinoheptulosonate 7-phosphate (DAHP) synthase () is the first enzyme in a series of metabolic reactions known as the shikimate pathway, which is responsible for the biosynthesis of the amino acids phenylalanine, tyrosine, and trypto ...

3-dehydroquinate synthase The enzyme 3-dehydroquinate synthase (EC 4.2.3.4) catalyzes the chemical reaction : 3-deoxy-D-''arabino''-hept-2-ulosonate 7-phosphate \rightleftharpoons 3-dehydroquinate + phosphate The protein uses NAD+ to catalyze the reaction. This react ...

, 3-dehydroquinate dehydratase,

shikimate dehydrogenase In enzymology, a shikimate dehydrogenase () is an enzyme that catalyzes the chemical reaction :shikimate + NADP+ \rightleftharpoons 3-dehydroshikimate + NADPH + H+ Thus, the two substrates of this enzyme are shikimate and NADP+, whereas it ...

shikimate kinase Shikimate kinase () is an enzyme that catalyzes the ATP-dependent phosphorylation of shikimate to form shikimate 3-phosphate. This reaction is the fifth step of the shikimate pathway, which is used by plants and bacteria to synthesize the commo ...

EPSP synthase 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase is an enzyme produced by plants and microorganisms. EPSPS catalyzes the chemical reaction: : phosphoenolpyruvate (PEP) + 3-phospho shikimate (S3P) phosphate + 5-enolpyruvylshikimate-3-phospha ...

, and chorismate synthase. The pathway starts with two substrates,

phosphoenol pyruvate Phosphoenolpyruvate (2-phosphoenolpyruvate, PEP) is the ester derived from the enol of pyruvate and phosphate. It exists as an anion. PEP is an important intermediate in biochemistry. It has the highest-energy phosphate bond found (−61.9 kJ/m ...

and

erythrose-4-phosphate Erythrose 4-phosphate is a phosphate of the simple sugar erythrose. It is an intermediate in the pentose phosphate pathway and the Calvin cycle. In addition, it serves as a precursor in the biosynthesis of the aromatic amino acids tyrosine, pheny ...

, and ends with

chorismate Chorismic acid, more commonly known as its anionic form chorismate, is an important biochemical intermediate in plants and microorganisms. It is a precursor for: * The aromatic amino acids phenylalanine, tryptophan, and tyrosine * Indole, indole ...

, a substrate for the three aromatic amino acids. The fifth

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

involved is the

, an enzyme that catalyzes the ATP-dependent phosphorylation of

shikimate Shikimic acid, more commonly known as its anionic form shikimate, is a cyclohexene, a cyclitol and a cyclohexanecarboxylic acid. It is an important biochemical metabolite in plants and microorganisms. Its name comes from the Japanese flower ''s ...

to form

shikimate 3-phosphate Shikimic acid, more commonly known as its anionic form shikimate, is a cyclohexene, a cyclitol and a cyclohexanecarboxylic acid. It is an important biochemical metabolite in plants and microorganisms. Its name comes from the Japanese flower ''shik ...

(shown in the figure below). Shikimate 3-phosphate is then coupled with

to give

5-enolpyruvylshikimate-3-phosphate 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase is an enzyme produced by plants and microorganisms. EPSPS catalyzes the chemical reaction: : phosphoenolpyruvate (PEP) + 3-phospho shikimate (S3P) phosphate + 5-enolpyruvylshikimate-3-phospha ...

via the enzyme 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase. Glycine phosphonate, more commonly known as Roundup, is a competitive inhibitor of EPSP synthase, acting as a transition state analog that binds more tightly to the EPSPS-S3P complex than PEP and inhibits the shikimate pathway. : Chorismate pathway 1

Then 5-enolpyruvylshikimate-3-phosphate is transformed into

by a chorismate synthase. : Chorismate pathway 2

Prephenic acid Prephenic acid, commonly also known by its anionic form prephenate, is an intermediate in the biosynthesis of the aromatic amino acids phenylalanine and tyrosine, as well as of a large number of secondary metabolites of the shikimate pathway. It ...

is then synthesized by a

Claisen rearrangement The Claisen rearrangement is a powerful carbon–carbon bond-forming chemical reaction discovered by Rainer Ludwig Claisen. The heating of an allyl vinyl ether will initiate a ,3sigmatropic rearrangement to give a γ,δ-unsaturated carbonyl, ...

by chorismate mutase. : Prephenate biosynthesis

Prephenate is oxidatively decarboxylated with retention of the

hydroxyl In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydro ...

group to give ''p''-hydroxyphenylpyruvate, which is transaminated using glutamate as the nitrogen source to give

and α-ketoglutarate. : Tyrosine biosynthesis

References

Bibliography

* * * * {{MetabolismMap Metabolic pathways