4-Hydroxybenzoic acid

It is found in plants of the genus Vitex such as V. agnus-castus or V. negundo, and in Hypericum perforatum (St John's wort). It is also found in Spongiochloris spongiosa, a freshwater green alga.

The compound is also found in Ganoderma lucidum, a medicinal mushroom with the longest record of use.

Cryptanaerobacter phenolicus is a bacterium species that produces benzoate from phenol via 4-hydroxybenzoate.{{cite journal|title=Cryptanaerobacter phenolicus gen. nov., sp. nov., an anaerobe that transforms phenol into benzoate via 4-hydroxybenzoate |first1=P. |last1=Juteau |first2=V. |last2=Côté |first3=M.-F. |last3=Duckett |first4=R. |last4=Beaudet |first5=F. |last5=Lépine |first6=R. |last6=Villemur |first7=J.-G. |last7=Bisaillon |journal=International Journal of Systematic and Evolutionary Microbiology |date=January 2005 |volume=55 |issue=1 |pages=245–250 |doi=10.1099/ijs.0.02914-0|pmid=15653882 |doi-access=free }}

4-Hydroxybenzoic acid can be found naturally in coconut.{{cite journal|title=Profiling C6–C3 and C6–C1 phenolic metabolites in Cocos nucifera |first1=G. |last1=Dey |first2=M. |last2=Chakraborty |first3=A. |last3=Mitra |journal=Journal of Plant Physiology |volume=162 |issue=4 |date=April 2005 |pages=375–381 |doi=10.1016/j.jplph.2004.08.006|pmid=15900879 }} It is one of the main catechins metabolites found in humans after consumption of green tea infusions.{{cite journal|title=Catechin metabolites after intake of green tea infusions |first1=P. G. |last1=Pietta |first2=P. |last2=Simonetti |first3=C. |last3=Gardana |first4=A. |last4=Brusamolino |first5=P. |last5=Morazzoni |first6=E. |last6=Bombardelli |journal=BioFactors |date=1998 |volume=8 |issue=1–2 |pages=111–118 |doi=10.1002/biof.5520080119|pmid=9699018 |s2cid=37684286 }} It is also found in wine,{{cite journal|title=Comparison of phenolic acids and flavan-3-ols during wine fermentation of grapes with different harvest times |first1=R.-R. |last1=Tian |first2=Q.-H. |last2=Pan |first3=J.-C. |last3=Zhan |first4=J.-M. |last4=Li |first5=S.-B. |last5=Wan |first6=Q.-H. |last6=Zhang |first7=W.-D. |last7=Huang |journal=Molecules |date=2009 |volume=14 |issue=2 |pages=827–838 |pmc=6253884 |doi=10.3390/molecules14020827|pmid=19255542 |doi-access=free }} in vanilla, in Macrotyloma uniflorum (horse gram), carob{{Cite journal | title=Functional Components of Carob Fruit: Linking the Chemical and Biological Space |pmc = 5133875|year = 2016|last1 = Goulas|first1 = V.|last2 = Stylos|first2 = E.|last3 = Chatziathanasiadou|first3 = M. V.|last4 = Mavromoustakos|first4 = T.|last5 = Tzakos|first5 = A. G.|journal = International Journal of Molecular Sciences|volume = 17|issue = 11|pages = 1875|pmid = 27834921|doi = 10.3390/ijms17111875| doi-access=free }} and in Phyllanthus acidus (Otaheite gooseberry).

Açaí oil, obtained from the fruit of the açaí palm (Euterpe oleracea), is rich in p-hydroxybenzoic acid ({{val|892|52|u=mg/kg}}).{{cite journal |journal = Journal of Agricultural and Food Chemistry |date=June 2008 | volume = 56 | issue = 12 | pages = 4631–4636 | title = Chemical composition, antioxidant properties, and thermal stability of a phytochemical enriched oil from Açaí (Euterpe oleracea Mart.) | last1 = Pacheco Palencia | first1 = L. A. | last2 = Mertens-Talcott | first2 = S. | last3 = Talcott | first3 = S. T. |pmid = 18522407| doi = 10.1021/jf800161u}} It is also found in cloudy olive oil{{citation needed|date=February 2019}} and in the edible mushroom Russula virescens (green-cracking russula).{{citation needed|date=February 2019}}

p-Hydroxybenzoic acid glucoside can be found in mycorrhizal and non-mycorrhizal roots of Norway spruces (Picea abies).{{cite journal|title=Phenolics of mycorrhizas and non-mycorrhizal roots of Norway spruce |first1=B. |last1=Münzenberger |first2=J. |last2=Heilemann |first3=D. |last3=Strack |first4=I. |last4=Kottke |first5=F. |last5=Oberwinkler |journal=Planta |year=1990 |volume=182 |issue=1 |pages=142–148 |doi=10.1007/BF00239996|pmid=24197010 |s2cid=43504838 }}

Violdelphin is an anthocyanin, a type of plant pigments, found in blue flowers and incorporating two p-hydroxybenzoic acid residues, one rutinoside and two glucosides associated with a delphinidin.

Agnuside is the ester of aucubin and p-hydroxybenzoic acid.{{cite journal | title = An analytical high performance liquid chromatographic method for the determination of agnuside and p-hydroxybenzoic acid contents in Agni-casti fructose | first1 = E. | last1 = Hoberg | first2 = B. | last2 = Meier | first3 = O. | last3 = Sticher | journal = Phytochemical Analysis | volume = 11 | issue = 5 | pages = 327–329 | date = September 2000 | doi = 10.1002/1099-1565(200009/10)11:5<327::AID-PCA523>3.0.CO;2-0| bibcode = 2000PChAn..11..327H }}

Chorismate lyase is an enzyme that transforms chorismate into 4-hydroxybenzoate and pyruvate. This enzyme catalyses the first step in ubiquinone biosynthesis in Escherichia coli and other Gram-negative bacteria.

Benzoate 4-monooxygenase is an enzyme that utilizes benzoate, NADPH, H⁺ and O₂ to produce 4-hydroxybenzoate, NADP⁺ and H₂O. This enzyme can be found in Aspergillus niger.

4-Hydroxybenzoate also arises from tyrosine.{{cite journal |doi=10.1016/j.bbabio.2016.03.036 |title=Coenzyme Q biosynthesis in health and disease |date=2016 |last1=Acosta |first1=Manuel Jesús |last2=Vazquez Fonseca |first2=Luis |last3=Desbats |first3=Maria Andrea |last4=Cerqua |first4=Cristina |last5=Zordan |first5=Roberta |last6=Trevisson |first6=Eva |last7=Salviati |first7=Leonardo |journal=Biochimica et Biophysica Acta (BBA) - Bioenergetics |volume=1857 |issue=8 |pages=1079–1085 |pmid=27060254 |doi-access=free }}

The enzyme 4-methoxybenzoate monooxygenase (O-demethylating) transforms 4-methoxybenzoate, an electron acceptor AH₂ and O₂ into 4-hydroxybenzoate, formaldehyde, the reduction product A and H₂O. This enzyme participates in 2,4-dichlorobenzoate degradation in Pseudomonas putida.

The enzyme 4-hydroxybenzaldehyde dehydrogenase uses 4-hydroxybenzaldehyde, NAD⁺ and H₂O to produce 4-hydroxybenzoate, NADH and H⁺. This enzyme participates in toluene and xylene degradation in bacteria such as Pseudomonas mendocina. It is also found in carrots (Daucus carota).

The enzyme that 2,4'-dihydroxyacetophenone dioxygenase transforms 2,4'-dihydroxyacetophenone and O₂ into 4-hydroxybenzoate and formate. This enzyme participates in bisphenol A degradation. It can be found in Alcaligenes species.

The enzyme 4-chlorobenzoate dehalogenase uses 4-chlorobenzoate and H₂O to produce 4-hydroxybenzoate and chloride. It can be found in Pseudomonas species.

The enzyme 4-hydroxybenzoyl-CoA thioesterase utilizes 4-hydroxybenzoyl-CoA and H₂O to produce 4-hydroxybenzoate and CoA. This enzyme participates in 2,4-dichlorobenzoate degradation. It can be found in Pseudomonas species.

The enzyme 4-hydroxybenzoate polyprenyltransferase uses a polyprenyl diphosphate and 4-hydroxybenzoate to produce diphosphate and 4-hydroxy-3-polyprenylbenzoate. This enzyme participates in ubiquinone biosynthesis.

The enzyme 4-hydroxybenzoate geranyltransferase utilizes geranyl diphosphate and 4-hydroxybenzoate to produce 3-geranyl-4-hydroxybenzoate and diphosphate. Biosynthetically, alkannin is produced in plants from the intermediates 4-hydroxybenzoic acid and geranyl pyrophosphate. This enzyme is involved in shikonin biosynthesis. It can be found in Lithospermum erythrorhizon.

The enzyme 3-hydroxybenzoate—CoA ligase uses ATP, 3-hydroxybenzoate and CoA to produce AMP, diphosphate and 3-hydroxybenzoyl-CoA. The enzyme works equally well with 4-hydroxybenzoate. It can be found in Thauera aromatica.

The enzyme 4-hydroxybenzoate 1-hydroxylase transforms 4-hydroxybenzoate, NAD(P)H, 2 H⁺ and O₂ into hydroquinone, NAD(P)⁺, H₂O and CO₂. This enzyme participates in 2,4-dichlorobenzoate degradation. It can be found in Candida parapsilosis.

The enzyme 4-hydroxybenzoate 3-monooxygenase transforms 4-hydroxybenzoate, NADPH, H⁺ and O₂ into protocatechuate, NADP⁺ and H₂O. This enzyme participates in benzoate degradation via hydroxylation and 2,4-dichlorobenzoate degradation. It can be found in Pseudomonas putida and Pseudomonas fluorescens.

The enzyme 4-hydroxybenzoate 3-monooxygenase (NAD(P)H) utilizes 4-hydroxybenzoate, NADH, NADPH, H⁺ and O₂ to produce 3,4-dihydroxybenzoate (protocatechuic acid), NAD⁺, NADP⁺ and H₂O. This enzyme participates in benzoate degradation via hydroxylation and 2,4-dichlorobenzoate degradation. It can be found in Corynebacterium cyclohexanicum and in Pseudomonas sp.

The enzyme 4-hydroxybenzoate decarboxylase uses 4-hydroxybenzoate to produce phenol and CO₂. This enzyme participates in benzoate degradation via coenzyme A (CoA) ligation. It can be found in Klebsiella aerogenes (Aerobacter aerogenes).

The enzyme 4-hydroxybenzoate—CoA ligase transforms ATP, 4-hydroxybenzoate and CoA to produce AMP, diphosphate and 4-hydroxybenzoyl-CoA. This enzyme participates in benzoate degradation via CoA ligation. It can be found in Rhodopseudomonas palustris.

Coniochaeta hoffmannii is a plant pathogen that commonly inhabits fertile soil. It is known to metabolize aromatic compounds of low molecular weight, such as p-hydroxybenzoic acid.

The enzyme 4-hydroxybenzoate 4-O-beta-D-glucosyltransferase transforms UDP-glucose and 4-hydroxybenzoate into UDP and 4-Hydroxybenzoic acid 4-O-glucoside. It can be found in the pollen of Pinus densiflora.

The Hammett equation describes a linear free-energy relationship relating reaction rates and equilibrium constants for many reactions involving benzoic acid derivatives with meta- and para-substituents.

4-Hydroxybenzoic acid is produced commercially from potassium phenoxide and carbon dioxide in the Kolbe-Schmitt reaction.Edwin Ritzer and Rudolf Sundermann "Hydroxycarboxylic Acids, Aromatic" in Ullmann's Encyclopedia of Industrial Chemistry 2002, Wiley-VCH, Weinheim. {{doi| 10.1002/14356007.a13_519}} It can also be produced in the laboratory by heating potassium salicylate with potassium carbonate to 240 °C, followed by treating with acid.{{OrgSynth | prep = CV2P0341 | first1 = C. A. | last1 = Buehler | first2 = W. E. | last2 = Cate | title = p-Hydroxybenzoic acid | collvol = 2 | collvolpages = 341 | year = 1943 }}

4-Hydroxybenzoic acid has about one tenth the acidity of benzoic acid, having an acid dissociation constant K_a = {{val|3.3e-5|u=M}} at 19 °C.{{citation needed|date=August 2012}} Its acid dissociation follows this equation:

:{{chem2|HOC6H4CO2H}} ⇌ {{chem2|HOC6H4CO2-}} + {{chem2|H+}}

Vectran is a manufactured fiber, spun from a liquid crystal polymer. Chemically it is an aromatic polyester produced by the polycondensation of 4-hydroxybenzoic acid and 6-hydroxynaphthalene-2-carboxylic acid. The fiber has been shown to exhibit strong radiation shielding used by Bigelow Aerospace and produced by StemRad.{{cite web | last=Charles Fishman | first=Dan Winters | title=This Expandable Structure Could Become the Future of Living in Space | website=Smithsonian Magazine | date=2016-04-11 | url=https://www.smithsonianmag.com/science-nature/robert-bigelow-visio-future-living-space-180958698/ | access-date=2020-12-07}}

4,4′-Dihydroxybenzophenone is generally prepared by the rearrangement of p-hydroxyphenylbenzoate. Alternatively, p-hydroxybenzoic acid can be converted to p-acetoxybenzoyl chloride. This acid chloride reacts with phenol to give, after deacetylation, 4,4′-dihydroxybenzophenone.

Examples of drugs made from PHBA include nifuroxazide, orthocaine, ormeloxifene and proxymetacaine.

4-Hydroxybenzoic acid is a popular antioxidant in part because of its low toxicity. The {{LD50}} is 2200 mg/kg in mice (oral).{{cite book | editor-last = Lewis | editor-first = R. J. | title = Sax's Dangerous Properties of Industrial Materials | edition = 9th | volume= 1–3 | location = New York, NY | publisher = Van Nostrand Reinhold | date = 1996 | pages = 2897}}

4-Hydroxybenzoic acid has estrogenic activity both in vitro and in vivo,{{cite book|first=S. K.|last=Khetan|title=Endocrine Disruptors in the Environment|url=https://books.google.com/books?id=s2ajAwAAQBAJ&pg=PT109|date=23 May 2014|publisher=Wiley|isbn=978-1-118-89115-5|page=109}} and stimulates the growth of human breast cancer cell lines.{{cite journal | last1 = Pugazhendhi |first1=D. |last2=Pope |first2=G. S. |last3=Darbre |first3=P. D. | title = Oestrogenic activity of p-hydroxybenzoic acid (common metabolite of paraben esters) and methylparaben in human breast cancer cell lines | journal = Journal of Applied Toxicology | volume = 25 | issue = 4 | pages = 301–309 | year = 2005 | pmid = 16021681 | doi = 10.1002/jat.1066 |s2cid=12342018 }}{{cite book|first=J.|last=Gabriel|title=Holistic Beauty from the Inside Out: Your Complete Guide to Natural Health, Nutrition, and Skincare|url=https://books.google.com/books?id=7BLtbCCwR74C&pg=PT31|date=April 2013|publisher=Seven Stories Press|isbn=978-1-60980-462-6|page=31}} It is a common metabolite of paraben esters, such as methylparaben. The compound is a relatively weak estrogen, but can produce uterotrophy with sufficient doses to an equivalent extent relative to estradiol, which is unusual for a weakly estrogenic compound and indicates that it may be a full agonist of the estrogen receptor with relatively low binding affinity for the receptor.{{cite journal | last1 = Lemini |first1=C. |last2=Silva |first2=G. |last3=Timossi |first3=C. |last4=Luque |first4=D. |last5=Valverde |first5=A. |last6=González Martínez |first6=M. |last7=Hernández |first7=A. |last8=Rubio Póo |first8=C. |last9=Chávez Lara |first9=B. |last10=Valenzuela |first10=F. | title = Estrogenic effects of p-hydroxybenzoic acid in CD1 mice | journal = Environmental Research | volume = 75 | issue = 2 | pages = 130–134 | year = 1997 | pmid = 9417843 | doi = 10.1006/enrs.1997.3782 | bibcode = 1997ER.....75..130L }}{{cite book|author=OECD|title=OECD Guidelines for the Testing of Chemicals / OECD Series on Testing and Assessment Detailed Background Review of the Uterotrophic Bioassay|url=https://books.google.com/books?id=nzfqBkSdgXgC&pg=PA183|date=November 2004|publisher=OECD Publishing|isbn=978-92-64-07885-7|page=183}} It is about 0.2% to 1% as potent as an estrogen as estradiol.

• Phenolic content in tea
• Phenolic content in wine

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{{phenolExplorer|418}}

{{Phenolic acid}}

{{Xenoestrogens}}

{{Estrogenics}}

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Category:Xenoestrogens

Category:Carboxylic acid-based monomers

Category:Monohydroxybenzoic acids

Category:Phenolic human metabolites