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Shikimic acid pathway

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SONALI GADGE

The document discusses the shikimic acid pathway, which is used by plants and microorganisms to synthesize aromatic amino acids from carbohydrates. It involves several enzymatic steps beginning with phosphoenolpyruvate and erythrose-4-phosphate that ultimately produce chorismate. Chorismate is then converted to prephenate and further transformed to produce phenylalanine, tyrosine, and tryptophan. The pathway is important for producing phenolic compounds, gallic acid, and other aromatic metabolites. Shikimic acid extracted from plants is used to produce the anti-influenza drug oseltamivir, and herbicides like glyphosate target enzymes in this pathway

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SHIKIMIC ACID PATHWAY Presented by Sonali S Gadge Lecturer P R Patil Institute of Pharmacy, Talegaon (SP), Dist-Wardha.
Phytoconstituents (Phyto=Plant and Constituents= Chemicals)  Living plants are solar powered biochemical and biosynthetic factory which manufactures both Primary and Secondary metabolites. Primary Metabolite Secondary Metabolite Widely distributed in nature practically in all organism. Biosynthetically derived from primary metabolite. It is more limited in distribution restricted in taxonomic group. Directly involved in growth, development and reproduction (like carbohydrates, proteins and fats) Not directly involved in growth and development. Involved in chemical adaption to environmental stress, serves as protective, defensive or offensive chemicals against microorganisms, insects and higher herbivorous animals. Generally non-expensive to produce (to isolate from plant/plant parts) ex-starch from potato. Generally expensive to produce. Ex- Quinine from cinchona bark. Present in plants in large quantity. Present in plants in much smaller quantity than primary metabolites.
Simple in nature. Complex in nature. Generally do not have only biological or pharmacological action (Therapeutic value). Have marked pharmacological action (therapeutic activity) on human body. Responsible for medicinal value of plants. Ex- Carbohydrates (Starch, Cellulose, Sugar) Lipids (Fatty acids) Proteins (Amino acids) Alkaloids, Glycosides, Flavonoids, Resin, Terpenoids. Ex- Quinine in Cinchona bark.
Introduction to basic metabolic pathway • The reaction sequence occurring within the organism in an orderly and regulated way known as metabolic pathway. Primary metabolic pathway of Carbon: A B C D
Shikimic acid pathway
Introduction to Shikimic acid Pathway  It is metabolic pathway for biosynthesis of Aromatic amino acid ( Phenyl alanine, Tyrosine and Tryptophan).  Shikimic acid pathway (Shikimate pathway), is a metabolic pathway used by bacteria, fungi, algae, some protozoans and plants for the biosynthesis of aromatic amino acids (Phenylalanine, tyrosine and tryptophan).  Shikimic acid is the key intermediate from carbohydrates for biosynthesis of C6-C3 unit (Phenyl propane derivative).  This pathway is not found in animals (including humans), who must instead obtain these essential amino acids from their diet.  This can be through either the direct consumption of plants or microorganisms or their indirect consumption via the consumption of other animals.
Enzymes involved in the Shikimate Pathway 1. DAHP Synthatase 2. 3-dehydroquinate dehydratase 3. Shikimate dehydrogenase 4. Shikimate kinase 5. EPSP Synthatase 6. Chorismate synthatase Biosynthetic Precursor 1. Phosphoenol pyruvate 2. Erythrose -4-phosphate 3. Nitrogen from other amino acids-Glutamate, Glycine, Serine
Shikimic acid  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 Shikimi, the Japanese star anise, Illicium anisatum from which it was isolated in 1885 by John Fredrick Eykman.  The elucidation of its structure was made nearly 50 years later.  Shikimic acid is also the glycoside part of some hydrolysable tannins.
Shikimic acid pathway
Shikimic acid pathway
• Phosphoenol pyruvate (From Glycolysis) and Erythrose-4-Phosphate (From Pentose phosphate pathway) react to form 2-keto3- deoxy7posphoglucoheptonic acid, in a reaction catalyzed by the enzyme DAHP Synthase. • 2-keto3-deoxy7phosphoglucoheptonic acid is then transferred to 3- dehydroquinate(DHQ), in a reaction catalyzed by DHQ Synthase. • DHQ is dehydrated to 3-dehydroshikimic acid by the enzyme 3- dehydroquinate dehydratase, which uses nicotinamide adenine dinucleotide phosphate (NADPH) as a cofactor. • The next enzyme Shikimate Kinase, an enzyme that catalyzes the ATP- dependent phosphorylation of shikimate to form shikimate 3-shikimate 3- phosphate. Shikimate phosphate is then coupled with phosphoenol pyruvate to give 5-enolpyruvylshikimate-3-phosphate via the enzyme 5- enolpyruvylshkimate-3-phosphate (EPSP) synthase. • Then 5-enolpyruvylshikimate-3-phosphate is transformed into chorismate by a Chorismate synthase. • Prephenic acid then synthesized by a Claisen rearrangment of chorismate by Chorismate mutase. • Prephenate is oxidatively decarboxylated with retention of the hydroxyl group by Prephenate dehydrogenase to give p-hydroxyphenylpyruvate, which is transaminated using glutamate as the nitrogen source to give tyrosine.
Role of Shikimic acid Pathway 1. Starting point in the biosynthesis of Phenolics Phenyl alanine and tyrosine are the precursors used in the biosynthesis of Phenylpropanoids. The Phenylpropanoids are then used to produce the flavonoids coumarins, tannins and lignin. 2. Gallic acid biosynthesis Gallic acid is formed from 3-dehydro-shikimate by the action of enzyme shikimate dehydrogenase to produce3,5-didehyroshikimate. The later compound spontaneously rearranges to gallic acid. 3. Other compounds • Shikimic acid is a precursor for: Indole, Indole derivatives and aromatic amino acids tryptophan and Tryptophan derivatives such as the psychedelic compound dimethyltryptamine. Many alkaloids and other aromatic metabolites.
Uses  In the pharmaceutical industry, shikimic acid from the Chinese star anise (Illicium verum) is used as a base material for production of Oseltamivir (Tamiflu). • Aminoshikimic acid is also an alternative to shikimic acid as a starting material for the synthesis of Oseltamivir. Target for Drugs  Shikimate can be used to synthesize (6S)-6-fluroshikimic acid, an antibiotic which inhibits the aromatic biosynthetic pathway. • Glyphosate, the active ingredient in the herbicide Roundup, kills plants by interfering with the shikimate pathway in plants. More specifically, glyphosate inhibits the enzyme 5-enolpyruvylshikimate-3-phosphate synthatase (EPSPS).
Shikimic acid pathway

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Shikimic acid pathway

  • 1. SHIKIMIC ACID PATHWAY Presented by Sonali S Gadge Lecturer P R Patil Institute of Pharmacy, Talegaon (SP), Dist-Wardha.
  • 2. Phytoconstituents (Phyto=Plant and Constituents= Chemicals)  Living plants are solar powered biochemical and biosynthetic factory which manufactures both Primary and Secondary metabolites. Primary Metabolite Secondary Metabolite Widely distributed in nature practically in all organism. Biosynthetically derived from primary metabolite. It is more limited in distribution restricted in taxonomic group. Directly involved in growth, development and reproduction (like carbohydrates, proteins and fats) Not directly involved in growth and development. Involved in chemical adaption to environmental stress, serves as protective, defensive or offensive chemicals against microorganisms, insects and higher herbivorous animals. Generally non-expensive to produce (to isolate from plant/plant parts) ex-starch from potato. Generally expensive to produce. Ex- Quinine from cinchona bark. Present in plants in large quantity. Present in plants in much smaller quantity than primary metabolites.
  • 3. Simple in nature. Complex in nature. Generally do not have only biological or pharmacological action (Therapeutic value). Have marked pharmacological action (therapeutic activity) on human body. Responsible for medicinal value of plants. Ex- Carbohydrates (Starch, Cellulose, Sugar) Lipids (Fatty acids) Proteins (Amino acids) Alkaloids, Glycosides, Flavonoids, Resin, Terpenoids. Ex- Quinine in Cinchona bark.
  • 4. Introduction to basic metabolic pathway • The reaction sequence occurring within the organism in an orderly and regulated way known as metabolic pathway. Primary metabolic pathway of Carbon: A B C D
  • 6. Introduction to Shikimic acid Pathway  It is metabolic pathway for biosynthesis of Aromatic amino acid ( Phenyl alanine, Tyrosine and Tryptophan).  Shikimic acid pathway (Shikimate pathway), is a metabolic pathway used by bacteria, fungi, algae, some protozoans and plants for the biosynthesis of aromatic amino acids (Phenylalanine, tyrosine and tryptophan).  Shikimic acid is the key intermediate from carbohydrates for biosynthesis of C6-C3 unit (Phenyl propane derivative).  This pathway is not found in animals (including humans), who must instead obtain these essential amino acids from their diet.  This can be through either the direct consumption of plants or microorganisms or their indirect consumption via the consumption of other animals.
  • 7. Enzymes involved in the Shikimate Pathway 1. DAHP Synthatase 2. 3-dehydroquinate dehydratase 3. Shikimate dehydrogenase 4. Shikimate kinase 5. EPSP Synthatase 6. Chorismate synthatase Biosynthetic Precursor 1. Phosphoenol pyruvate 2. Erythrose -4-phosphate 3. Nitrogen from other amino acids-Glutamate, Glycine, Serine
  • 8. Shikimic acid  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 Shikimi, the Japanese star anise, Illicium anisatum from which it was isolated in 1885 by John Fredrick Eykman.  The elucidation of its structure was made nearly 50 years later.  Shikimic acid is also the glycoside part of some hydrolysable tannins.
  • 11. • Phosphoenol pyruvate (From Glycolysis) and Erythrose-4-Phosphate (From Pentose phosphate pathway) react to form 2-keto3- deoxy7posphoglucoheptonic acid, in a reaction catalyzed by the enzyme DAHP Synthase. • 2-keto3-deoxy7phosphoglucoheptonic acid is then transferred to 3- dehydroquinate(DHQ), in a reaction catalyzed by DHQ Synthase. • DHQ is dehydrated to 3-dehydroshikimic acid by the enzyme 3- dehydroquinate dehydratase, which uses nicotinamide adenine dinucleotide phosphate (NADPH) as a cofactor. • The next enzyme Shikimate Kinase, an enzyme that catalyzes the ATP- dependent phosphorylation of shikimate to form shikimate 3-shikimate 3- phosphate. Shikimate phosphate is then coupled with phosphoenol pyruvate to give 5-enolpyruvylshikimate-3-phosphate via the enzyme 5- enolpyruvylshkimate-3-phosphate (EPSP) synthase. • Then 5-enolpyruvylshikimate-3-phosphate is transformed into chorismate by a Chorismate synthase. • Prephenic acid then synthesized by a Claisen rearrangment of chorismate by Chorismate mutase. • Prephenate is oxidatively decarboxylated with retention of the hydroxyl group by Prephenate dehydrogenase to give p-hydroxyphenylpyruvate, which is transaminated using glutamate as the nitrogen source to give tyrosine.
  • 12. Role of Shikimic acid Pathway 1. Starting point in the biosynthesis of Phenolics Phenyl alanine and tyrosine are the precursors used in the biosynthesis of Phenylpropanoids. The Phenylpropanoids are then used to produce the flavonoids coumarins, tannins and lignin. 2. Gallic acid biosynthesis Gallic acid is formed from 3-dehydro-shikimate by the action of enzyme shikimate dehydrogenase to produce3,5-didehyroshikimate. The later compound spontaneously rearranges to gallic acid. 3. Other compounds • Shikimic acid is a precursor for: Indole, Indole derivatives and aromatic amino acids tryptophan and Tryptophan derivatives such as the psychedelic compound dimethyltryptamine. Many alkaloids and other aromatic metabolites.
  • 13. Uses  In the pharmaceutical industry, shikimic acid from the Chinese star anise (Illicium verum) is used as a base material for production of Oseltamivir (Tamiflu). • Aminoshikimic acid is also an alternative to shikimic acid as a starting material for the synthesis of Oseltamivir. Target for Drugs  Shikimate can be used to synthesize (6S)-6-fluroshikimic acid, an antibiotic which inhibits the aromatic biosynthetic pathway. • Glyphosate, the active ingredient in the herbicide Roundup, kills plants by interfering with the shikimate pathway in plants. More specifically, glyphosate inhibits the enzyme 5-enolpyruvylshikimate-3-phosphate synthatase (EPSPS).