# Protopine

> Mediated Wiki article. Canonical URL: https://mediated.wiki/source/Protopine
> Markdown URL: https://mediated.wiki/source/Protopine.md
> Source: https://en.wikipedia.org/wiki/Protopine
> Source revision: 1339192619
> License: Creative Commons Attribution-ShareAlike 4.0 International (https://creativecommons.org/licenses/by-sa/4.0/)

{{Chembox
| ImageFile = Protopine structure.svg
| ImageClass = skin-invert-image
| ImageSize = 
| ImageFile1 = Protopine-from-xtal-Mercury-3D-balls.png
| ImageClass1 = bg-transparent
| IUPACName = 7-Methyl-2′''H'',2′′''H''-7,13a-secobis([1,3]dioxolo)[4′,5′:2,3;4′′,5′′:9,10]berbin-13a-one
| SystematicName = 5-Methyl-4,6,7,14-tetrahydro-2''H'',10''H''-bis([1,3]benzodioxolo)[4,5-''c'':5′,6′-''g'']azecin-13(5''H'')-one
| Reference = <ref>{{cite book|title=The Merck Index|publisher=Merck & Co|location=New Jersey|year=1976|edition=9|page=1023}}</ref>
|Section1={{Chembox Identifiers
| CASNo_Ref = {{cascite|correct|??}}
| CASNo = 130-86-9
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = UIW569HT35
| PubChem = 4970
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 453019<!--486179 different isomer, inchi does not match--> 
| SMILES = c15cc3OCOc3cc5CCN(C)Cc2c(CC1=O)ccc4c2OCO4
| EINECS = 204-999-6
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4799
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C20H19NO5/c1-21-5-4-13-7-18-19(25-10-24-18)8-14(13)16(22)6-12-2-3-17-20(15(12)9-21)26-11-23-17/h2-3,7-8H,4-6,9-11H2,1H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = GPTFURBXHJWNHR-UHFFFAOYSA-N
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 16415
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C05189
}}
|Section2={{Chembox Properties
| Formula = C<sub>20</sub>H<sub>19</sub>NO<sub>5</sub>
| MolarMass = 353.369 g/mol
| Appearance = white crystals
| Density = 1.399 g/cm<sup>3</sup>
| MeltingPtC = 208
| BoilingPt =
| Solubility = practically insoluble
| SolubleOther = 1:15
| Solvent = [chloroform](/source/chloroform)
}}
}}

'''Protopine''' is an [alkaloid](/source/alkaloid) occurring in [opium poppy](/source/opium_poppy),<ref>[http://www.thefreedictionary.com/Protopine The Free Dictionary: Protopine]</ref> ''[Corydalis](/source/Corydalis)'' tubers<ref>{{cite journal |doi=10.1016/j.ejphar.2004.11.004|pmid=15588728 |year=2004 |last1=Jiang |first1=B |last2=Cao |first2=K |last3=Wang |first3=R |title=Inhibitory effect of protopine on K(ATP) channel subunits expressed in HEK-293 cells.|volume=506|issue=2|pages=93–100|journal=European Journal of Pharmacology}}</ref> and other plants of the family [papaveraceae](/source/papaveraceae), like ''[Fumaria officinalis](/source/Fumaria_officinalis)''.<ref>{{cite journal |last1= Vrba |first1= Jiri |last2= Vrublova |first2= Eva |last3= Modriansky |first3= Martin |last4= Ulrichova |first4= Jitka |title= Protopine and allocryptopine increase mRNA levels of cytochromes P450 1A in human hepatocytes and HepG2 cells independently of AhR |journal= Toxicology Letters |date= 2011 |volume= 203 |issue= 2 |pages= 135–141 |doi= 10.1016/j.toxlet.2011.03.015 |pmid= 21419197 }}</ref> 

It has been found to inhibit [histamine H1 receptor](/source/histamine_H1_receptor)s and [platelet aggregation](/source/platelet_aggregation), and acts as an [analgesic](/source/analgesic).<ref>{{cite journal|pmid=9368908|year=1997|last1=Saeed|first1=SA|last2=Gilani|last3=Majoo|last4=Shah|title=Anti-thrombotic and anti-inflammatory activities of protopine.|volume=36|issue=1|pages=1–7|doi=10.1006/phrs.1997.0195|journal=Pharmacological Research|first2=AH|first3=RU|first4=BH}}</ref><ref>{{MeshName|Protopine}}</ref>

==Biosynthesis==
Protopine is derived in the plants such as the opium poppy, ''[Papaver somniferum](/source/Papaver_somniferum)'', from the [benzylisoquinoline alkaloid](/source/Benzylisoquinoline_alkaloids) (''S'')-[reticuline](/source/reticuline) through a progressive series of five enzymatic transformations: 1) [berberine bridge enzyme](/source/BBE-like_enzymes) to [(''S'')-scoulerine](/source/scoulerine); 2) [(''S'')-cheilanthifoline synthase](/source/(S)-cheilanthifoline_synthase)/CYP719A25 to [(''S'')-cheilanthifoline](/source/(S)-cheilanthifoline); 3)&nbsp; [(''S'')-stylopine synthase](/source/(S)-stylopine_synthase)/CYP719A20 to (''S'')-[stylopine](/source/stylopine); 4) (''S'')-tetrahydroprotoberberine ''N''-methyltransferase to (''S'')-''cis''-''N''-methylstylopine.<ref>{{Cite journal|last=Hagel|first=Jillian M|last2=Morris|first2=Jeremy S|last3=Lee|first3=Eun-Jeong|last4=Desgagne-Penix|first4=Isabel|last5=Bross|first5=Crystal D|last6=Chang|first6=Limei|last7=Chen|first7=Xue|last8=Farrow|first8=Scott C|last9=Zhang|first9=Ye|date=2015|title=Transcriptome analysis of 20 taxonomically related benzylisoquinoline alkaloid-producing plants|url=http://openlib.tugraz.at/download.php?id=564f2fa60a35b&location=browse|journal=BMC Plant Biology|volume=15|pages=227|doi=10.1186/s12870-015-0596-0| pmc=4575454 |pmid=26384972|doi-access=free}}</ref> 

The final step is [oxidation](/source/redox) by the enzyme [methyltetrahydroprotoberberine 14-monooxygenase](/source/methyltetrahydroprotoberberine_14-monooxygenase):<ref name=NPR>{{cite journal |last1=Tian |first1=Ya |last2=Kong |first2=Lingzhe |last3=Li |first3=Qi |last4=Wang |first4=Yifan |last5=Wang |first5=Yongmiao |last6=An |first6=Zhoujie |last7=Ma |first7=Yuwei |last8=Tian |first8=Lixia |last9=Duan |first9=Baozhong |last10=Sun |first10=Wei |last11=Gao |first11=Ranran |last12=Chen |first12=Shilin |last13=Xu |first13=Zhichao |title=Structural diversity, evolutionary origin, and metabolic engineering of plant specialized benzylisoquinoline alkaloids |journal=Natural Product Reports |date=2024 |volume=41 |issue=11 |pages=1787–1810 |doi=10.1039/d4np00029c |pmid=39360417 }}</ref><ref>{{cite journal |vauthors=Rueffer M, Zenk MH | date = 1987 |title=Enzymatic formation of protopines by a microsomal cytochrome-P-450 system of Corydalis vaginans |journal=Tetrahedron Lett. |volume=28 |pages=5307–5310 |doi=10.1016/S0040-4039(00)96715-7 |issue=44 |url=http://nbn-resolving.de/urn:nbn:de:bvb:19-epub-3622-0 }}</ref>

{{chemrxn|width=60%|
{{chemrxn/cpd|qid=Q27105298|caption=(''S'')-''cis''-N-methylstylopine }}
{{chemrxn/txt|+ [NADPH](/source/NADPH) }}
{{chemrxn/arw|fwd_in={{chem2|O2}}|fwd_out={{chem2|H2O}} }}
{{chemrxn/cpd|protopine }}
{{chemrxn/txt|+ [NADP+](/source/NADP%2B) }}
}}

==Metabolism==
The enzyme [protopine 6-monooxygenase](/source/protopine_6-monooxygenase) converts protopine into dihydrosanguinarine.<ref name=NPR/><ref>{{cite journal |last1=Tanahashi |first1=Takao |last2=Zenk |first2=Meinhart H. |title=Elicitor induction and characterization of microsomal protopine-6-hydroxylase, the central enzyme in benzophenanthridine alkaloid biosynthesis |journal=Phytochemistry |date=1990 |volume=29 |issue=4 |pages=1113–1122 |doi=10.1016/0031-9422(90)85414-B }}</ref> NADP<sup>+</sup> and water are the by-products.

{{chemrxn|width=60%|
{{chemrxn/cpd|protopine }}
{{chemrxn/txt|+ [NADPH](/source/NADPH) }}
{{chemrxn/arw|fwd_in={{chem2|O2}}|fwd_out={{chem2|H2O}} }}
{{chemrxn/cpd|dihydrosanguinarine }}
{{chemrxn/txt|+ [NADP<sup>+</sup>](/source/NADP%2B) }}
}}

The enzyme uses reduced [nicotinamide adenine dinucleotide phosphate](/source/nicotinamide_adenine_dinucleotide_phosphate) (NADPH), and oxygen, with the initial product being 6-hydroxyprotopine, which spontaneously forms dihydrosanguinarine, found in plants such as ''[Sanguinaria canadensis](/source/Sanguinaria_canadensis)''.<ref>{{cite journal |last1=Ignatov |first1=Atanas |last2=Clark |first2=W.Gregg |last3=Cline |first3=Steven D. |last4=Psenak |first4=Mikulas |last5=Krueger |first5=Robert J. |last6=Coscia |first6=Carmine J. |title=Elicitation of dihydrobenzophenanthridine oxidase in Sanguinaria canadensis cell cultures |journal=Phytochemistry |date=1996 |volume=43 |issue=6 |pages=1141–1144 |doi=10.1016/S0031-9422(96)00540-7 |pmid=8987906 }}</ref>

== See also ==
* [Cryptopine](/source/Cryptopine)
* [Bürgi-Dunitz angle](/source/B%C3%BCrgi-Dunitz_angle)

== References ==
{{reflist}}
{{Components of Opium}}

Category:Alkaloids found in Papaveraceae
Category:Natural opium alkaloids
Category:Methylenedioxyphenethylamines
Category:Heterocyclic compounds with 5 rings
Category:Benzodioxoles
Category:Azecines

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