# Prephenic acid

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> Markdown URL: https://mediated.wiki/source/Prephenic_acid.md
> Source: https://en.wikipedia.org/wiki/Prephenic_acid
> Source revision: 1331861016
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{{chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 464214063
| ImageFile = Prephenic acid.svg
| ImageSize = 150px
| ImageFile1 = Prephenic-acid-based-on-PDB-3ZP7-3D-bs-17.png
| ImageSize1 = 150px
| PIN = (1''s'',4''s'')-1-(2-Carboxy-2-oxoethyl)-4-hydroxycyclohexa-2,5-diene-1-carboxylic acid
| OtherNames = Prephenate; ''cis''-1-Carboxy-4-hydroxy-α-oxo-2,5-cyclohexadiene-1-propanoic acid
|Section1={{Chembox Identifiers
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 16735981
| InChI = 1/C10H10O6/c11-6-1-3-10(4-2-6,9(15)16)5-7(12)8(13)14/h1-4,6,11H,5H2,(H,13,14)(H,15,16)/t6-,10+
| InChIKey = FPWMCUPFBRFMLH-XGAOUMNUBN
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C10H10O6/c11-6-1-3-10(4-2-6,9(15)16)5-7(12)8(13)14/h1-4,6,11H,5H2,(H,13,14)(H,15,16)/t6-,10+
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = FPWMCUPFBRFMLH-XGAOUMNUSA-N
| CASNo = 126-49-8
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo_Comment = (unspecified)
| CASNo1 = 87664-40-2
| CASNo1_Ref = {{cascite|correct|CAS}}
| CASNo1_Comment = (''cis'')
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = Z66B98Z97I
| UNII_Comment = (unspecified)
| PubChem = 1028
| PubChem_Comment = (unspecified)
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 84387
| SMILES = O=C(O)[C@@]/1(CC(=O)C(O)=O)\C=C/[C@@H](O)\C=C\1
| MeSHName = Prephenic+acid
}}
|Section2={{Chembox Properties
| C=10 | H=10 | O=6
| Appearance=
| Density=
| MeltingPt=
| BoilingPt=
| Solubility=
}}
}}

'''Prephenic acid''', commonly also known by its [anionic](/source/ion) form '''prephenate''', is an intermediate in the [biosynthesis](/source/biosynthesis) of the aromatic [amino acid](/source/amino_acid)s [phenylalanine](/source/phenylalanine) and [tyrosine](/source/tyrosine), as well as of a large number of [secondary metabolites](/source/secondary_metabolites) of the [shikimate pathway](/source/shikimate_pathway).

== Occurrence and biological significance ==
Prephenic acid occurs naturally as an intermediate in the [biosynthesis](/source/biosynthesis) of [phenylalanine](/source/phenylalanine) and [tyrosine](/source/tyrosine) via the [shikimic acid pathway](/source/shikimic_acid_pathway).<ref name=":0">{{citation|author=Richard G.H. Cotton, Frank Gibson |date=April 1965 |doi=10.1016/0304-4165(65)90429-0 |issue=1 |pages=76–88 |periodical=Biochimica et Biophysica Acta (BBA) - General Subjects |title=The biosynthesis of phenylalanine and tyrosine; enzymes converting chorismic acid into prephenic acid and their relationships to prephenate dehydratase and prephenate dehydrogenase |volume=100|pmid=14323651 }}<!-- auto-translated from German by Module:CS1 translator --></ref><ref name=":1">{{citation|author=H. Plieninger |date=July 1962 |doi=10.1002/anie.196203671 |issue=7 |pages=367–372 |periodical=Angewandte Chemie International Edition in English |title=Prephenic Acid: Properties and the Present Status of its Synthesis |volume=1}}<!-- auto-translated from German by Module:CS1 translator --></ref> It is formed from [chorismic acid](/source/chorismic_acid) by [chorismate mutase](/source/chorismate_mutase):<ref>{{cite journal |vauthors = Kast P, Grisostomi C, Chen IA, Li S, Krengel U, Xue Y, Hilvert D |title = A strategically positioned cation is crucial for efficient catalysis by chorismate mutase |journal = The Journal of Biological Chemistry |volume = 275 |issue = 47 |pages = 36832–8 |date = November 2000 |pmid = 10960481 |doi = 10.1074/jbc.M006351200 |doi-access = free }}</ref>

The biosynthesis involves a [3,3]-[sigmatropic](/source/Sigmatropic_reaction) [Claisen rearrangement](/source/Claisen_rearrangement) of chorismic acid.<ref>{{cite journal
 | title = On the mechanism of the chorismate mutase reaction |author = Helmut Goerisch |journal = [Biochemistry](/source/Biochemistry_(journal))
 | year = 1978 |pages = 3700–3705 |doi = 10.1021/bi00611a004 |volume = 17 |issue = 18| pmid = 100134 }}</ref><ref>{{cite journal 
 | title = Thermodynamics of the Conversion of Chorismate to Prephenate: Experimental Results and Theoretical Predictions |author = Peter Kast, Yadu B. Tewari, Olaf Wiest, Donald Hilvert, [Kendall N. Houk](/source/Kendall_Newcomb_Houk), and Robert N. Goldberg |journal = J. Phys. Chem. B |volume = 101 |issue = 50 |pages = 10976–10982 | year = 1997 |doi = 10.1021/jp972501l}}</ref>

:350px

Prephenic acid can be [dehydrated](/source/dehydrated) by [prephenate dehydratase](/source/prephenate_dehydratase) to phenylpyruvic acid, which is a precursor of phenylalanine.<ref>{{KEGG enzyme|4.2.1.51}}</ref><ref>{{cite journal | vauthors = Cotton RG, Gibson F | title = The biosynthesis of phenylalanine and tyrosine; enzymes converting chorismic acid into prephenic acid and their relationships to prephenate dehydratase and prephenate dehydrogenase | date = 1965 | journal = Biochim. Biophys. Acta  | volume = 100 | pages = 76&ndash;88  | pmid = 14323651 | doi=10.1016/0304-4165(65)90429-0}}</ref>

{{chemrxn|width=40%|
{{chemrxn/cpd|prephenic acid }}
{{chemrxn/arw|direction=reversible|fwd_out={{chem2|CO2 + H2O}}|rev_in={{chem2|CO2 + H2O}} }}
{{chemrxn/cpd|phenylpyruvic acid }}
}}

Alternatively, it can be [decarboxylated](/source/decarboxylated) and oxidised by [prephenate dehydrogenase](/source/prephenate_dehydrogenase) to give [4-hydroxyphenylpyruvic acid](/source/4-hydroxyphenylpyruvic_acid), which is a precursor of tyrosine:<ref name=":0" /><ref>{{cite journal |vauthors=Gamborg OL, Keeley FW | date = 1966 | title = Aromatic metabolism in plants. I. A study of the prephenate dehydrogenase from bean plants | journal = Biochim. Biophys. Acta  | volume = 115 | pages = 65&ndash;72  | pmid = 4379953 | issue = 1 | doi=10.1016/0304-4165(66)90049-3}}</ref>

{{chemrxn|width=50%|
{{chemrxn/cpd|Prephenic acid|caption=prephenic acid }}
{{chemrxn/txt|+ [NADP<sup>+</sup>](/source/NADP%2B)}}
{{chemrxn/arw|direction=reversible|fwd_out={{chem2|CO2 + H+}}|rev_in={{chem2|CO2 + H+}} }}
{{chemrxn/cpd|4-Hydroxyphenylpyruvic acid|caption=4-hydroxyphenylpyruvic acid }}
{{chemrxn/txt|+ [NADPH](/source/NADPH)}}
}}

== Synthesis ==
Prephenic acid is unstable; as a [1,4-cyclohexadiene](/source/1%2C4-cyclohexadiene), it is easily [aromatized](/source/aromatized), for example, under the influence of acids or bases. This instability makes both isolation and synthesis difficult. Prephenic acid was first isolated from mutants of ''[Escherichia coli](/source/Escherichia_coli)'' that were unable to convert prephenic acid to [phenylpyruvic acid](/source/phenylpyruvic_acid). During this process, the [barium](/source/barium) salt was obtained.<ref name=":1" />

== Stereochemistry ==
Prephenic acid is an example of achiral (optically inactive) molecule which has two [pseudoasymmetric](/source/pseudoasymmetric) atoms (''i.e.'' [stereogenic](/source/Stereocenter) but not [chirotopic](/source/chirotopic) centers), the C1 and the C4 [cyclohexadiene](/source/cyclohexadiene) ring atoms. It has been shown<ref>{{Cite journal|last1=Danishefsky|first1=Samuel|last2=Hirama|first2=Masahiro|last3=Fritsch|first3=Nancy|last4=Clardy|first4=Jon|date=1979-11-01|title=Synthesis of disodium prephenate and disodium epiprephenate. Stereochemistry of prephenic acid and an observation on the base-catalyzed rearrangement of prephenic acid to p-hydroxyphenyllactic acid|journal=Journal of the American Chemical Society|volume=101|issue=23|pages=7013–7018|doi=10.1021/ja00517a039|bibcode=1979JAChS.101.7013D |issn=0002-7863}}</ref> that of the two possible [diastereoisomers](/source/Diastereomer), the natural prephenic acid is one that has both substituents at higher priority (according to [CIP](/source/Cahn%E2%80%93Ingold%E2%80%93Prelog_priority_rules) rules) on the two pseudoasymmetric carbons, ''i.e.'' the carboxyl and the hydroxyl groups, in the ''cis'' configuration, or (1''s'',4''s'') according to the new IUPAC stereochemistry rules (2013).<ref>{{Cite book|title=Nomenclature of Organic Chemistry|last1=Favre|first1=Henri A|last2=Powell|first2=Warren H|date=2013-12-17|isbn=9780854041824|language=en|doi=10.1039/9781849733069}}</ref>

The other stereoisomer, ''i.e. trans'' or, better, (1''r'',4''r''), is called '''epiprephenic'''.

==See also==
* [C<sub>10</sub>H<sub>10</sub>O<sub>6</sub>](/source/C10H10O6)

==References==
{{Reflist}}

Category:Hydroxycarboxylic acids
Category:Alpha-keto acids
Category:Dicarboxylic acids
Category:Cyclohexadienes

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Adapted from the Wikipedia article [Prephenic acid](https://en.wikipedia.org/wiki/Prephenic_acid) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Prephenic_acid?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.