{{chembox | Watchedfields = changed | verifiedrevid = 477165260 | ImageFile=Protocatechusäure.svg | ImageSize=120px | PIN=3,4-Dihydroxybenzoic acid | ImageFile1 = 3,4-Dihydroxybenzoic acid.jpg | OtherNames = 3,4-Dihydroxybenzoic acid<br>PCA<br>Protocatechuate |Section1={{Chembox Identifiers | CASNo_Ref = {{cascite|correct|CAS}} | CASNo=99-50-3 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 36R5QJ8L4B | PubChem=72 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 37537 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 71 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB03946 | EINECS = 202-760-0 | KEGG = C00230 | 3DMet = B00064 | RTECS = UL0560000 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 36062 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C7H6O4/c8-5-2-1-4(7(10)11)3-6(5)9/h1-3,8-9H,(H,10,11) | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = YQUVCSBJEUQKSH-UHFFFAOYSA-N | SMILES=C1=CC(=C(C=C1C(=O)O)O)O }} |Section2={{Chembox Properties | Properties_ref=<ref name=crc>{{cite book |editor=Haynes, William M. |date=2016 |title=CRC Handbook of Chemistry and Physics |edition=97th |publisher=CRC Press |chapter=3 |page=190 |url=https://ia800704.us.archive.org/27/items/CRCHandbookOfChemistryAndPhysics97thEdition2016/CRC%20Handbook%20of%20Chemistry%20and%20Physics%20-%2097th%20Edition%20%282016%29.pdf?page=3-190 |isbn=9781498754293}}</ref> | C=7 |H=6 |O=4 | Appearance= light brown solid | Density={{val|1.524|u=g/cm3}} ({{convert|4|C|F K}}) | MeltingPtC= 202 | MeltingPt_ref = | BoilingPtC = | Solubility= {{ubl |{{val|18|u=g/L}} ({{convert|14|C|F K}}) |{{val|271|u=g/L}} ({{convert|80|C|F K}})<ref name=crcCh5>{{cite book |editor=Haynes, William M. |date=2016 |title=CRC Handbook of Chemistry and Physics |edition=97th |publisher=CRC Press |chapter=5 |url=https://ia800704.us.archive.org/27/items/CRCHandbookOfChemistryAndPhysics97thEdition2016/CRC%20Handbook%20of%20Chemistry%20and%20Physics%20-%2097th%20Edition%20%282016%29.pdf |isbn=9781498754293}}</ref>{{rp|5-148}} }} | Solubility1 = very soluble | Solvent1 = ethanol | Solubility2 = soluble | Solvent2 = diethyl ether | pKa = {{ubl |4.48 |8.83 |12.6<ref name=crcCh5/>{{rp|5-91}} }} }} |Section3={{Chembox Hazards | ExternalSDS = [http://www.sigmaaldrich.com/MSDS/MSDS/DisplayMSDSPage.do?country=PL&language=EN-generic&productNumber=37580&brand=ALDRICH&PageToGoToURL=http%3A//www.sigmaaldrich.com/catalog/product/aldrich/37580%3Flang%3Dpl MSDS] | MainHazards= | FlashPt= | AutoignitionPt = | NFPA-H = 2 | NFPA-F = 0 | NFPA-R = 0 }} |Section8={{Chembox Related |OtherCompounds = {{ubl |2,3-Dihydroxybenzoic acid |2,4-Dihydroxybenzoic acid |2,5-Dihydroxybenzoic acid |2,6-Dihydroxybenzoic acid |3,5-Dihydroxybenzoic acid |Ethyl protocatechuate }} }} }} thumb|right|UV visible spectrum of protocatechuic acid '''Protocatechuic acid''' ('''PCA''') is a dihydroxybenzoic acid, a type of phenolic acid. It is a major metabolite of antioxidant polyphenols found in green tea. It has mixed effects on normal and cancer cells in ''in vitro'' and ''in vivo'' studies.<ref>{{cite journal |last1=Lin |first1=H.-H. |last2=Chen |first2=J.-H. |last3=Huang |first3=C.-C. |last4=Wang |first4=C.-J. |title=Apoptotic effect of 3,4-dihydroxybenzoic acid on human gastric carcinoma cells involving JNK/p38 MAPK signaling activation |journal= International Journal of Cancer |volume=120 |issue=11 |pages=2306–2316 |date=June 2007 |pmid=17304508 |doi=10.1002/ijc.22571 |doi-access=free }}</ref> It is produced commercially from vanillin.<ref>{{Ullmann| doi=10.1002/14356007.a13_519| chapter=Hydroxycarboxylic Acids, Aromatic|year=2000| last1=Ritzer| first1=Edwin| last2=Sundermann| first2=Rudolf| isbn=3527306730}}</ref>
== Biological effects == Protocatechuic acid (PCA) is antioxidant and anti-inflammatory. PCA extracted from ''Hibiscus sabdariffa'' protected against chemically induced liver toxicity ''in vivo''. ''In vitro'' testing documented antioxidant and anti-inflammatory activity of PCA, while liver protection ''in vivo'' was measured by chemical markers and histological assessment.<ref name="hibo">{{cite journal |last1=Liu |first1=C.-L. |last2=Wang |first2=J.-M. |last3=Chu |first3=C.-Y. |title=In vivo protective effect of protocatechuic acid on ''tert''-butyl hydroperoxide-induced rat hepatotoxicity |journal=Food and Chemical Toxicology |volume=40 |pages=635–41 |year=2002 |pmid=11955669 |last4=Cheng |first4=M.-T. |last5=Tseng |first5=T.-H. |issue=5 |doi=10.1016/s0278-6915(02)00002-9}}</ref>
PCA has been reported to induce apoptosis of human leukemia cells, as well as malignant HSG1 cells taken from human oral cavities,<ref>{{cite journal |last1=Babich |first1=H. |last2=Sedletcaia |first2=A. |last3=Kenigsberg |first3=B. |title=''In vitro'' cytotoxicity of protocatechuic acid to cultured human cells from oral tissue: involvement in oxidative stress |journal=Pharmacology & Toxicology |volume=91 |issue=5 |pages=245–253 |date=November 2002 |pmid=12570031 |doi=10.1034/j.1600-0773.2002.910505.x |doi-access=free }}</ref> but PCA was found to have mixed effects on TPA-induced mouse skin tumours. Depending on the amount of PCA and the time before application, PCA could reduce or enhance tumour growth.<ref>{{cite journal |last1=Nakamura |first1=Y. |last2=Torikai |first2=K. |last3=Ohto |first3=Y. |last4=Murakami |first4=A. |last5=Tanaka |first5=T. |last6=Ohigashi |first6=H. |title=A simple phenolic antioxidant protocatechuic acid enhances tumor promotion and oxidative stress in female ICR mouse skin: dose- and timing-dependent enhancement and involvement of bioactivation by tyrosinase |journal=Carcinogenesis |volume=21 |issue=10 |pages=1899–1907 |date=October 2000 |pmid=11023549 |doi= 10.1093/carcin/21.10.1899|doi-access=free }}</ref> Similarly, PCA was reported to increase proliferation and inhibit apoptosis of neural stem cells.<ref>{{cite journal |last1=Guan |first1=S. |last2=Ge |first2=D. |last3=Liu |first3=T. Q. |last4=Ma |first4=X.-H. |last5=Cui |first5=Z.-F. |date=March 2009 |title= Protocatechuic acid promotes cell proliferation and reduces basal apoptosis in cultured neural stem cells|journal= Toxicology in Vitro|volume= 23|issue= 2|pages=201–208 |pmid= 19095056 |doi= 10.1016/j.tiv.2008.11.008|bibcode=2009ToxVi..23..201G }}</ref> In an ''in vitro'' model using HL-60 leukemia cells, protocatechuic acid showed an antigenotoxic effect and tumoricidal activity.<ref>{{cite journal|last1=Anter |first1=J. |last2=Romero Jiménez |first2=M. |last3=Fernández Bedmar |first3=Z. |last4=Villatoro Pulido |first4=M. |last5=Analla |first5=M. |last6=Alonso Moraga |first6=A. |last7=Muñoz Serrano |first7=A. |title=Antigenotoxicity, cytotoxicity, and apoptosis induction by apigenin, bisabolol, and protocatechuic acid |journal=Journal of Medicinal Food |date=March 2011 |volume=14 |issue=3 |pages=276–283|doi=10.1089/jmf.2010.0139 |pmid=21182433 }}</ref> In two preclinical investigations, protocatechuic acid from ''Hibiscus sabdariffa'' showed an excellent ability to effectively inhibit the replication of herpes simplex virus type 2<ref>{{cite journal|last1=Hassan |first1=S. T. S. |last2=Švajdlenka |first2=E. |last3=Berchová-Bímová |first3=K. |title=''Hibiscus sabdariffa'' L. and its bioactive constituents exhibit antiviral activity against HSV-2 and anti-enzymatic properties against urease by an ESI–MS based assay |journal=Molecules |date=April 2017 |volume=22 |issue=5 |page=722|doi=10.3390/molecules22050722 |pmid=28468298 |pmc=6154344 |doi-access=free }}</ref> and to potently deactivate the catalytic activity of urease.<ref>{{cite journal|last1=Hassan |first1=S. T. S. |last2=Švajdlenka |first2=E. |title=Biological evaluation and molecular docking of protocatechuic acid from ''Hibiscus sabdariffa'' L. as a potent urease inhibitor by an ESI–MS based method|journal=Molecules|date=October 2017 |volume=22 |issue=10 |page=1696|doi=10.3390/molecules22101696 |pmid=29019930 |pmc=6151788 |doi-access=free }}</ref>
== Occurrence in nature == Protocatechuic acid can be isolated from the stem bark of ''Boswellia dalzielii''.<ref>{{cite journal|title=Antibacterial phenolics from ''Boswellia dalzielii'' |last1=Alemika |first1=T. E. |last2=Onawunmi |first2=G. O. |last3=Olugbade |first3=T. O. |journal=Nigerian Journal of Natural Products and Medicines |date=2006 |volume=10 |pages=108–110 |url=http://dspace.unijos.edu.ng/handle/10485/1174 |archive-url=https://web.archive.org/web/20130730080304/http://dspace.unijos.edu.ng/handle/10485/1174 |url-status=dead |archive-date=2013-07-30 |access-date=2013-07-30 }}</ref> and from leaves of ''Diospyros melanoxylon''.<ref>{{cite journal|last1=Mallavadhani |first1=U. V. |last2=Mahapatra |first2=A. |title=A new aurone and two rare metabolites from the leaves of ''Diospyros melanoxylon'' |journal=Natural Product Research |date=2005 |volume=19 |issue=1 |pages=91–97|doi=10.1080/14786410410001704705 |pmid=15700652 |s2cid=35200920 }}</ref>
The hardening of the protein component of insect cuticle has been shown to be due to the tanning action of an agent produced by oxidation of a phenolic substance. In the analogous hardening of the cockroach ootheca, the phenolic substance concerned is protocatechuic acid.<ref>{{Cite journal | last1 = Hackman | first1 = R. H. | last2 = Pryor | first2 = M. G. | last3 = Todd | first3 = A. R. | title = The occurrence of phenolic substances in arthropods | journal = The Biochemical Journal | volume = 43 | issue = 3 | pages = 474–477 | year = 1948 | pmid = 16748434 | pmc = 1274717 | doi=10.1042/bj0430474 }}</ref>
=== In foods === Açaí oil, obtained from the fruit of the açaí palm (''Euterpe oleracea''), is rich in protocatechuic acid ({{val|630|36|u=mg/kg}}).<ref>{{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.) |pmid = 18522407| doi = 10.1021/jf800161u |last1=Pacheco Palencia |first1=L. A. |last2=Mertens-Talcott |first2=S |last3=Talcott |first3=S. T. }}</ref> Protocatechuic acid also exists in the skins of some strains of onion as an antifungal mechanism, increasing endogenous resistance against smudge fungus. It is also found in ''Allium cepa'' (17,540 ppm).<ref>{{Cite web |url=http://www.ars-grin.gov/cgi-bin/duke/highchem.pl |title=Chemical Query |access-date=2011-09-25 |archive-url=https://web.archive.org/web/20130616093128/http://www.ars-grin.gov/cgi-bin/duke/highchem.pl |archive-date=2013-06-16 |url-status=dead }}</ref>
PCA occurs in roselle (''Hibiscus sabdariffa''), which is used worldwide as a food and beverage.<ref name="hibo" />
Protocatechuic acid is also found in mushrooms such as ''Agaricus bisporus''<ref>{{cite journal |last1=Delsignore |first1=A |last2=Romeo. |first2=F. |last3=Giaccio |first3=M. |title=Content of phenolic substances in basidiomycetes |journal=Mycological Research |volume=101 |pages=552–556 |year=1997 |doi=10.1017/S0953756296003206 |issue=5}}</ref> or ''Phellinus linteus''.<ref name="pmid18827365">{{cite journal |doi=10.1248/bpb.31.1968 |last1=Lee |first1=Y.-S. |last2=Kang |first2=Y. H. |last3=Jung |first3=J. Y. |display-authors=etal |title=Protein glycation inhibitors from the fruiting body of ''Phellinus linteus'' |journal=Biological & Pharmaceutical Bulletin |volume=31 |issue=10 |pages=1968–72 |date=October 2008 |pmid=18827365 |doi-access=free }}</ref>
PCA is regarded as an active component in traditional Chinese herbal medicine such as Stenoloma chusanum (L.) Ching, Ilex chinensis Sims, Cibotium barometz (L.) J.Sm.<ref>{{Cite journal|last1=Li|first1=Xican|last2=Wang|first2=Xiaozhen|last3=Chen|first3=Dongfeng|last4=Chen|first4=Shuzhi|date=2011-07-31|title=Antioxidant Activity and Mechanism of Protocatechuic Acid in vitro|url=https://ffhdj.com/index.php/ffhd/article/view/127|journal=Functional Foods in Health and Disease|volume=1|issue=7|pages=232|doi=10.31989/ffhd.v1i7.127|issn=2160-3855|doi-access=free}}</ref>
== Metabolism == Protocatechuic acid is one of the main catechins metabolites found in humans after consumption of green tea infusions.<ref>{{cite journal | last1 = Pietta | first1 = P. G. | last2 = Simonetti | first2 = P. | last3 = Gardana | first3 = C. | last4 = Brusamolino | first4 = A. | last5 = Morazzoni | first5 = P. | last6 = Bombardelli | first6 = E. | year = 1998 | title = Catechin metabolites after intake of green tea infusions | journal = BioFactors | volume = 8 | issue = 1–2| pages = 111–118 | doi = 10.1002/biof.5520080119 | pmid=9699018| s2cid = 37684286 }}</ref>
=== Enzymes === ;Biosynthesis enzymes * 3-dehydroshikimate dehydratase * (3''S'',4''R'')-3,4-dihydroxycyclohexa-1,5-diene-1,4-dicarboxylate dehydrogenase * terephthalate 1,2-''cis''-dihydrodiol dehydrogenase * 3-hydroxybenzoate 4-monooxygenase * 4-hydroxybenzoate 3-monooxygenase (NAD(P)H) * 4-sulfobenzoate 3,4-dioxygenase * vanillate monooxygenase * 3,4-dihydroxyphthalate decarboxylase * 4,5-dihydroxyphthalate decarboxylase
center|thumb|600px|Protocatechuic acid biosynthesis
; Degradation enzymes * The enzyme protocatechuate decarboxylase uses 3,4-dihydroxybenzoate to produce catechol and {{chem2|CO2}}. * The enzyme protocatechuate 3,4-dioxygenase uses 3,4-dihydroxybenzoate and oxygen to produce 3-carboxy-''cis'',''cis''-muconate.<ref>{{cite journal |last1= Fujisawa |first1= H. |last2= Hayaishi |first2= O. |title= Protocatechuate 3,4-Dioxygenase |journal= Journal of Biological Chemistry |date= 1968 |volume= 243 |issue= 10 |pages= 2673–2681 |doi= 10.1016/S0021-9258(18)93425-3 |doi-access= free }}</ref>
{{chemrxn|width=40%| {{chemrxn/cpd|protocatechuic acid }} {{chemrxn/arw|fwd_in={{chem2|O2}} }} {{chemrxn/cpd|3-Carboxy-cis,cis-muconic acid|upright=2|caption=3-carboxy-''cis'',''cis''-muconic acid }} }}
== References == {{reflist}}
{{Phenolic acid}}
Category:Dihydroxybenzoic acids Category:Phenol antioxidants Category:Catechols