shikimic acid pathway B pharm 5th semester
- 2. INTRODUCTION The shikimic acid is a key intermediate from carbohydrate for the biosynthesis of C6-C3 units. Precursor for the synthesis of amino acid. Shikimic acid pathway is an alternate route to aromatic compounds, mainly the L-phenylalanine, L-tyrosine and L- tryptophan aromatic amino acids. This pathway is used by the microorganism and plants. Shikimic acid is a compound isolated from the plants of Illicium species, and is the central intermediate of this pathway. 2
- 3. 1. Conversion of Erythrose-4-phosphate to 3- Dehydroquine acid 3-Deoxy-D-Arabino-Heptulosonic acid-7-phosphate (DAHP) is formed when the precursors D-erythrose-4-phosphate and phosphoenolpyruvate combine. This reaction is catalysed by phospho-2-oxo-3-deoxyheptonate aldolase. The 3-dehydroquinate synthase enzyme catalyses the cyclization of DAHP to 3-dehydroquinic acid and needs cobalt (II) and Nicotinamide adenine dinucleotide (NAD) as co-factor. 3
- 4. 2. Formation of shikimic acid Dehydroquinic acid converts to quinic acid or 3- dehydroshikimic acid, which continue the pathway and produces shikimic acid. 3. Formation of chorismic acid After phosphorylation, catalysed by shikimate kinase enzymes, shikimic acid attaches to enol pyruvate to form 3- enolpyruvylshikimic acid 5-phosphate. Enolpyruvylshikimate phosphate synthase enzyme catalyses this reaction. Chorismate synthase enzyme catalyses its conversion to chorismic acid. 4
- 5. 4. Formation of other intermediates Chorismic acid converts to anthranilic acid in the presence of glutamine, whereas the formation of prephenic acid is catalysed by chorismate mutase enzyme. Chorismic acid is also converted to p-aminobenzoic acid. 5
- 6. 6 5. Formation of aromatic amino acids Anthranilic acid converts to phosphoribosylanthranilic acid (anthranilate phosphoribosyl transferase) and then to carboxyphenylaminodeoxyribulose-5-phosphate (carboxyphenylaminodeoxyribulose-5-phosphate). Ring closure to form indolyl-3-glycerol phosphate is catalysed by indolylglycerol phosphate synthase. Tryptophan synthase enzyme catalyses the final reaction and has two components: the first is component A that catalyses the dissociation of indolylglycerol phosphate to indol and glyceraldehyde-3-phosphate and the second is component B that catalyses the direct condensation of indole with serine to tryptophan.
- 7. Prephenic acid biosynthesises tyrosine and phenylalanine through independent pathways. During tyrosine formation, firstly prephenic acid is aromatised to 4- hydroxyphenylpyruvic acid. This reaction is catalysed by prephenate dehydrogenase enzyme. Then transamination occur to form tyrosine. This is catalysed by tyrosine aminotransferase enzyme. Biosynthesis of phenylalanine involves aromatisation of prephenic acid to phenylpyruvic acid and transamination to phenylalanine (phenylalanine aminotransferase enzyme). 7
- 8. ROLE OF SHIKIMIC ACID PATHWAY Shikimic acid is the starting points in the biosynthesis of many phenolic compound. Through shikimic acid pathway phenylalanine and tyrosine are obtained which act as a precursor for the biosynthesis of phenylpropanoids. The phenylpropanoids are then used to produce flavonoids, coumarins, lignin and tannins. Shikimic acid pathway is also helpful in Gallic acid biosynthesis. Gallic acid is formed from 3-dehydroshikimate in the presence of enzyme shikimate dehydrogenase and produces 3,5- didehydroshikimate which rearrange and gives Gallic acid. Shikimic acid pathway also involved in the biosynthesis of other compounds like Indole, Indole derivates and aromatic amino acid derivatives, many alkaloids and other metabolic metabolites. 8
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