Theshikimate pathway (shikimic acid pathway) is a seven-stepmetabolic pathway used bybacteria,archaea,fungi,algae, someprotozoans, andplants for thebiosynthesis offolates andaromatic amino acids (tryptophan,phenylalanine, andtyrosine). This pathway is not found in mammals.
The five enzymes involved in the shikimate pathway are3-dehydroquinate dehydratase,shikimate dehydrogenase,shikimate kinase,EPSP synthase, andchorismate synthase. In bacteria and eurkaryotes, the pathway starts with twosubstrates,phosphoenol pyruvate anderythrose-4-phosphate, are processed byDAHP synthase and3-dehydroquinate synthase to form3-dehydroquinate. In archaea,2-amino-3,7-dideoxy-D-threo-hept-6-ulosonate synthase condensesL-Aspartic-4-semialdehyde with a sugar to form 2-amino-3,7-dideoxy-D-threo-hept-6-ulosonate, which is then turned by3-dehydroquinate synthase II into 3-dehydroquinate. Both pathways end withchorismate (chrorismic acid), a substrate for the three aromatic amino acids. The fifthenzyme involved is theshikimate kinase, an enzyme that catalyzes theATP-dependentphosphorylation ofshikimate to formshikimate 3-phosphate (shown in the figure below).[1][2] Shikimate 3-phosphate is then coupled withphosphoenol pyruvate to give5-enolpyruvylshikimate-3-phosphate via the enzyme5-enolpyruvylshikimate-3-phosphate (EPSP) synthase.Glyphosate, the herbicidal ingredient inRoundup, 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.
Then 5-enolpyruvylshikimate-3-phosphate is transformed intochorismate by achorismate synthase.
Prephenic acid is then synthesized by aClaisen rearrangement ofchorismate bychorismate mutase.[3][4]
Prephenate isoxidatively decarboxylated with retention of thehydroxyl group to givep-hydroxyphenylpyruvate, which istransaminated usingglutamate as the nitrogen source to givetyrosine andα-ketoglutarate.
References
edit- ^Morar, Mariya; White, Robert H.; Ealick, Steven E. (1 September 2007). "Structure of 2-Amino-3,7-dideoxy- d - threo -hept-6-ulosonic Acid Synthase, a Catalyst in the Archaeal Pathway for the Biosynthesis of Aromatic Amino Acids ,".Biochemistry.46 (37):10562–10571.doi:10.1021/bi700934v.
- ^Herrmann, K. M.; Weaver, L. M. (1999). "The Shikimate Pathway".Annual Review of Plant Physiology and Plant Molecular Biology.50:473–503.doi:10.1146/annurev.arplant.50.1.473.PMID 15012217.
- ^Helmut Goerisch (1978). "On the mechanism of the chorismate mutase reaction".Biochemistry.17 (18):3700–3705.doi:10.1021/bi00611a004.PMID 100134.
- ^Peter Kast; Yadu B. Tewari; Olaf Wiest; Donald Hilvert;Kendall N. Houk; Robert N. Goldberg (1997). "Thermodynamics of the Conversion of Chorismate to Prephenate: Experimental Results and Theoretical Predictions".J. Phys. Chem. B.101 (50):10976–10982.doi:10.1021/jp972501l.
Bibliography
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- Edwin Haslam (1993).Shikimic Acid: Metabolism and Metabolites (1st ed.).ISBN 0471939994.
- Brown, Stewart A.; Neish, A. C. (1955). "Shikimic Acid as a Precursor in Lignin Biosynthesis".Nature.175 (4459):688–689.Bibcode:1955Natur.175..688B.doi:10.1038/175688a0.ISSN 0028-0836.PMID 14370198.S2CID 4273320.
- Weinstein, L. H.; Porter, C. A.; Laurencot, H. J. (1962). "Role of the Shikimic Acid Pathway in the Formation of Tryptophan in Higher Plants : Evidence for an Alternative Pathway in the Bean".Nature.194 (4824):205–206.Bibcode:1962Natur.194..205W.doi:10.1038/194205a0.ISSN 0028-0836.S2CID 4160308.
- Wilson, D J; Patton, S; Florova, G; Hale, V; Reynolds, K A (1998)."The shikimic acid pathway and polyketide biosynthesis".Journal of Industrial Microbiology and Biotechnology.20 (5):299–303.doi:10.1038/sj.jim.2900527.ISSN 1367-5435.S2CID 41117722.