Ficain

{{Short description|Class of enzymes}} {{Infobox enzyme | Name = Ficain | EC_number = 3.4.22.3 | CAS_number = 9001-33-6 | GO_code = | image = 4YYQ.pdb.png | width = | caption = Crystallographic structure of ficain from ''Ficus carica'', rainbow colored, N-terminus blue, C-terminus red. }} '''Ficain''' also known as '''ficin''', '''debricin''', or '''higueroxyl delabarre''' ({{EC number|3.4.22.3}}) is a proteolytic enzyme extracted from the latex sap from the stems, leaves, and unripe fruit of the American wild fig tree ''Ficus insipida''.<ref name=Swiss>{{cite web |url=https://www.qmul.ac.uk/sbcs/iubmb/enzyme/EC3/4/22/3.html |title=ENZYME 3.4.22.3 ficain |author= |website=Expasy - Swiss Bioinformatics Resource Portal |publisher=Swiss Institute of Bioinformatics |access-date=22 May 2021}}</ref><ref name="Perelló_2000"/><ref name=webmd/><ref>{{cite book | title = Proteolytic Enzymes | vauthors = Liener IE, Friedenson B | chapter = Ficin |series = Methods Enzymol. |date = 1970 |volume = 19 |pages = 261–273 |doi=10.1016/0076-6879(70)19020-3| isbn = 978-0-12-181881-4 }}</ref>

Ficain was originally called ficin, and ficin was originally a mixture of closely related cysteine endopeptidases produced from any species of the genus ''Ficus'', before the terminology was restricted to a specific cysteine endopeptidase enzyme from a specific species.

Cysteine endopeptidases are a group of enzymes that also include the more distantly related papain derived from papaya latex, bromelase (bromelain) extracted from pineapple stem, calpain, caspases, cathepsin B, and chymopapain.<ref name="Brocklehurst_1987">{{cite book | chapter = Cysteine proteinases | title = New Comprehensive Biochemistry: Hydrolytic Enzymes | vauthors = Brocklehurst K, Willenbrock F, Salih E |date = 1987 |pages = 39–158 | veditors = Neuberger A, Brocklehurst K |publisher = Elsevier |location = Amsterdam }}</ref> Cysteine endopeptidases with similar properties known generically as ficins are present in other members of the genus ''Ficus'', and many species appear to contain multiple types of these enzymes. Somewhat confusingly, the terms ficain and ficin are often treated as synonyms.

Ficain is in the MEROPS clan CA, family C1, subfamily C1A, peptidase C01.006.<ref name="Brocklehurst_1987"/>

== Nomenclature ==

The name ficin was first used by Robbins in 1930 to describe a purified substance with anthelmintic activity isolated from any member of the fig genus.<ref name = "Singleton_2013">{{cite book | vauthors = Singleton A, Buttle DJ | chapter = Ficain | title = Handbook of Proteolytic Enzymes | volume = 2: Metallopeptidases and Cysteine Peptidases | date = January 2013 | pages = 1877–9 | publisher = Academic Press | doi = 10.1016/B978-0-12-382219-2.00427-0 | isbn = 978-0-12-382219-2 }}</ref> The Enzyme Commission of the International Union of Biochemistry and Molecular Biology (IUBMB) originally assigned EC 3.4.4.12 as ficin in 1961, which was transferred to 3.4.22.3 and renamed to ficain in 1972, making the two term synonymous at the time.<ref name = "IUBMB">{{cite web |url=https://www.qmul.ac.uk/sbcs/iubmb/enzyme/EC3/4/22/3.html | title = EC 3.4.22.3 |author= |date= |website=IUBMB Enzyme Nomenclature |publisher=International Union of Biochemistry and Molecular Biology |access-date=22 May 2021}}</ref> Because the proteolytic enzymes from other members of the genus ''Ficus'' have not been fully characterized, the IUBMB in 1992 recommended the term ficain be restricted to the specific main proteolytic enzyme found in the ficin powder produced from ''F. glabrata'',<ref name="Perelló_2000"/> a taxon which has since been synonymised with ''F. insipida''.<ref name="POWO_853024-1">{{cite web |title=''Ficus insipida'' Willd. |work=Plants of the World Online |publisher=Royal Botanic Gardens, Kew|url=https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:853024-1 |access-date=2020-10-09 }}</ref> However IUBMB Enzyme Nomenclature database continues to list ficin as a synonym of ficain<ref name = "IUBMB" /> and the two terms are often used interchangeably.

== Applications ==

Purified ficin is a white powder that was first produced in 1930. It was initially observed how intestinal nematodes dissolved in a ficin solution, which arose interest in the product at the time as an anthelmintic, although it was not widely adopted.<ref name="Perelló_2000">{{cite journal | vauthors = Arribére MP, Caffin O, Priolo S |date=2000 |title=Proteolytic Enzymes from the Latex of ''Ficus pumila'' L. (Moraceae) |url=http://www.latamjpharm.org/trabajos/19/4/LAJOP_19_4_1_3_1Z237U2573.pdf |journal=Acta Farmacéutica Bonaerense |volume=19 |issue=4 |pages=257–262 |doi= |access-date=22 May 2021}}</ref> Purified ficin is not actually 'pure', it is a mix of different enzymes and can be produced from many different species of ''Ficus''.<ref name="Perelló_2000"/> A commonly used ficin is made from the latex of the common fig and consists of a mixture of several isoforms.<ref name="Brocklehurst_1987"/><ref name=Vatić2020>{{cite journal | vauthors = Vatić S, Mirković N, Milošević JR, Jovčić B, Polović NĐ | title = Broad range of substrate specificities in papain and fig latex enzymes preparations improve enumeration of Listeria monocytogenes | journal = International Journal of Food Microbiology | volume = 334 | issue = 108851 | article-number = 108851 | date = December 2020 | pmid = 32911158 | doi = 10.1016/j.ijfoodmicro.2020.108851 }}</ref> Up to ten different proteolytic enzymes were found in one study from that species alone,<ref name="Perelló_2000"/> and it even appears that different cultivars of common fig contain different ratios of these enzymes.<ref>{{cite journal | vauthors = Zare H, Moosavi-Movahedi AA, Salami M, Mirzaei M, Saboury AA, Sheibani N | title = Purification and autolysis of the ficin isoforms from fig (Ficus carica cv. Sabz) latex | journal = Phytochemistry | volume = 87 | pages = 16–22 | date = March 2013 | pmid = 23312458 | pmc = 3755362 | doi = 10.1016/j.phytochem.2012.12.006 | bibcode = 2013PChem..87...16Z }}</ref> The milky sap of the common fig also contains furanocoumarins (psoralen), although oddly enough these are found chiefly in the sap of the leaves and shoots, but not in the sap of the fruits.<ref name="Zaynoun et al. 1984">{{cite journal | vauthors = Zaynoun ST, Aftimos BG, Abi Ali L, Tenekjian KK, Khalidi U, Kurban AK | title = Ficus carica; isolation and quantification of the photoactive components | journal = Contact Dermatitis | volume = 11 | issue = 1 | pages = 21–5 | date = July 1984 | pmid = 6744838 | doi = 10.1111/j.1600-0536.1984.tb00164.x }} Cited in McGovern and Barkley 2000, section [http://telemedicine.org/botanica/bot5.htm Phytophotodermatitis].</ref> One factor which may account for this is that psoralen and other furanocoumarins are primarily deterrents against herbivory, acting as photosensitizing agents to induce phytophotodermatitis. Psoralen's absence in fruit sap is consistent with the fact that the fruit of endozoochorous plants represents a relatively rare instance where herbivory is ''encouraged'' by the plant.

Although later research found it to be ineffective and potentially unhealthy as an anthelmintic,<ref name="Perelló_2000"/><ref name=webmd>{{cite web |url=https://www.webmd.com/vitamins/ai/ingredientmono-141/ficin |title=Ficin |author= |date=2021 |website=Vitamins & Supplements |publisher=WebMD LLC |access-date=22 May 2021}}</ref> it later found numerous medical and industrial uses. It is used for cleaning in the production of stitching material for sutures, to prepare animal arteries before transplantation into humans,<ref name=webmd/> and for unmasking antigens in serology.<ref name="Perelló_2000"/> It is one of the most commonly used substances for differentiating many blood group antigens: For example, it destroys M, N, S, Duffy a, and Duffy b, and enhances some other antigens including antigens from the Rh, Kidd, Lewis, I, and P1 systems.<ref name="Brocklehurst_1987"/>

It is also used for cleaning the animal intestines used as sausage or cheese-casings. It is used as an additive to make freeze-resistant beer, and has been added to certain formulations of meat tenderizers along with related protease-type enzymes.<ref name=webmd/> For example, as a tenderizer it can be added to the meat in the production of bologna sausage, which improves some measurable quality attributes of the final product.<ref>{{cite journal | vauthors = Ramezani R, Aminlari M, Fallahi H |date=July 2006 |title=Effect of Chemically Modified Soy Proteins and Ficin-tenderized Meat on the Quality Attributes of Sausage |journal=Journal of Food Science |volume=68 |issue=1 |pages=85–88 |doi=10.1111/j.1365-2621.2003.tb14119.x}}</ref> It can be used for dissolving the proteins in meat products in order to release potentially present food-borne pathogenic bacteria for safety analysis. Latex from ''Ficus carica'' also appears to contain an enzyme which shows marked ability to digest collagen, as opposed to papain.<ref name=Vatić2020/> This, however, is not a cysteine protease, but a serine protease.<ref>{{cite journal | vauthors = Nishimura K, Higashiya K, Ueshima N, Kojima K, Takita T, Abe T, Takahashi T, Yasukawa K | display-authors = 6 | title = Insight into the collagen-degrading activity of a serine protease in the latex of Ficus carica cultivar Masui Dauphine | journal = Bioscience, Biotechnology, and Biochemistry | volume = 85 | issue = 5 | pages = 1147–1156 | date = April 2021 | pmid = 33580958 | doi = 10.1093/bbb/zbab025 | doi-access = free }}</ref>

The crude, unrefined latex of ''F. insipida'' is also sold in North and South American as an anthelmintic herbal medicine called 'doctor oje' (''ojé'' in Brazil).<ref name=webmd/><ref name="Hansson_2005">{{cite journal | vauthors = Hansson A, Zelada JC, Noriega HP | title = Reevaluation of risks with the use of Ficus insipida latex as a traditional anthelmintic remedy in the Amazon | journal = Journal of Ethnopharmacology | volume = 98 | issue = 3 | pages = 251–7 | date = April 2005 | pmid = 15814256 | doi = 10.1016/j.jep.2004.12.029 }}</ref> The crude latex is toxic, overdoses due to use as a medicine are possible and occur rarely, but it remains a popular drug in certain regions.<ref name="Hansson_2005"/> During the 1940s the substance was known by medical practitioners as ''leche de higuerón'', and it was considered to be the most effective treatment for trichuriasis at the time.<ref>{{cite journal |author= | title=Clinical Aspects and Treatment of the More Common Intestinal Parasites of Man (TB-33) | journal=Veterans Administration Technical Bulletin 1946 & 1947 | year=1948 | volume=10 | pages=1–14 | url=https://books.google.com/books?id=uJWxEzwqRiMC }}</ref> Species used in the production of ''leche de higuerón'' in the 1920s included ''F. glaborata'' and ''F. laurifolia''.<ref>{{cite book|title=The American Journal of Tropical Medicine|url=https://books.google.com/books?id=3HVMAQAAMAAJ&pg=PA377|year=1921|publisher=Williams and Wilkins|page=377}}</ref>

== References == {{reflist}}

== External links == * {{MeshName|Ficain}} * {{EC number|3.4.22.3}}

Category:EC 3.4.22 Category:Fibrinolytic enzymes