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Ficain

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Ficain
Crystallographic structure of ficain fromFicus carica,rainbow colored, N-terminus blue, C-terminus red.
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EC no.3.4.22.3
CAS no.9001-33-6
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Ficainalso known asficin,debricin,orhigueroxyl delabarre(EC3.4.22.3) is aproteolyticenzyme extracted from thelatexsap from the stems, leaves, and unripe fruit of the American wild fig treeFicus insipida.[1][2][3][4]

Ficain was originally called ficin, and ficin was originally a mixture of closely relatedcysteine endopeptidasesproduced from any species of the genusFicus,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 relatedpapainderived from papaya latex, bromelase (bromelain) extracted from pineapple stem,calpain,caspases,cathepsin B,andchymopapain.[5]Cysteine endopeptidases with similar properties known generically as ficins are present in other members of the genusFicus,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 theMEROPSclan CA, family C1, subfamily C1A, peptidase C01.006.[5]

Nomenclature

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The name ficin was first used by Robbins in 1930 to describe a purified substance withanthelminticactivity isolated from any member of the fig genus.[6]The Enzyme Commission of theInternational 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.[7]Because the proteolytic enzymes from other members of the genusFicushave 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 fromF. glabrata,[2]ataxonwhich has since beensynonymisedwithF. insipida.[8]However IUBMB Enzyme Nomenclature database continues to list ficin as a synonym of ficain[7]and the two terms are often used interchangeably.

Applications

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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 ananthelmintic,although it was not widely adopted.[2]Purified ficin is not actually 'pure', it is a mix of different enzymes and can be produced from many different species ofFicus.[2]A commonly used ficin is made from the latex of thecommon figand consists of a mixture of several isoforms.[5][9]Up to ten different proteolytic enzymes were found in one study from that species alone,[2]and it even appears that differentcultivarsof common fig contain different ratios of these enzymes.[10]The milky sap of the common fig also containsfuranocoumarins(psoralen), although oddly enough these are found chiefly in the sap of the leaves and shoots, but not in the sap of the fruits.[11]One factor which may account for this is that psoralen and other furanocoumarins are primarily deterrents against herbivory, acting asphotosensitizing agentsto inducephytophotodermatitis.Psoralen's absence in fruit sap is consistent with the fact that the fruit ofendozoochorousplants represents a relatively rare instance where herbivory isencouragedby the plant.

Although later research found it to be ineffective and potentially unhealthy as an anthelmintic,[2][3]it later found numerous medical and industrial uses. It is used for cleaning in the production of stitching material forsutures,to prepare animalarteriesbefore transplantation into humans,[3]and for unmaskingantigensinserology.[2]It is one of the most commonly used substances for differentiating manyblood group antigens:For example, it destroysM, N, S,Duffya, and Duffy b, and enhances some other antigens including antigens from the Rh, Kidd, Lewis, I, and P1 systems.[5]

It is also used for cleaning the animal intestines used assausage or cheese-casings.It is used as an additive to makefreeze-resistantbeer, and has been added to certain formulations ofmeat tenderizersalong with relatedprotease-type enzymes.[3]For example, as a tenderizer it can be added to the meat in the production ofbologna sausage,which improves some measurable quality attributes of the final product.[12]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 fromFicus caricaalso appears to contain an enzyme which shows marked ability to digestcollagen,as opposed to papain.[9]This, however, is not a cysteine protease, but aserine protease.[13]

The crude, unrefined latex ofF. insipidais also sold in North and South American as ananthelminticherbal medicinecalled 'doctor oje' (ojéin Brazil).[3][14]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.[14]During the 1940s the substance was known by medical practitioners asleche de higuerón,and it was considered to be the most effective treatment fortrichuriasisat the time.[15]Species used in the production ofleche de higuerónin the 1920s includedF. glaborataandF. laurifolia.[16]

References

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  1. ^"ENZYME 3.4.22.3 ficain".Expasy - Swiss Bioinformatics Resource Portal.Swiss Institute of Bioinformatics.Retrieved22 May2021.
  2. ^abcdefgArribére MP, Caffin O, Priolo S (2000)."Proteolytic Enzymes from the Latex ofFicus pumilaL. (Moraceae) "(PDF).Acta Farmacéutica Bonaerense.19(4): 257–262.Retrieved22 May2021.
  3. ^abcde"Ficin".Vitamins & Supplements.WebMD LLC. 2021.Retrieved22 May2021.
  4. ^Liener IE, Friedenson B (1970).Ficin.Methods Enzymol. Vol. 19. pp. 261–273.doi:10.1016/0076-6879(70)19020-3.ISBN978-0-12-181881-4.
  5. ^abcdBrocklehurst K, Willenbrock F, Salih E (1987). "Cysteine proteinases". In Neuberger A, Brocklehurst K (eds.).New Comprehensive Biochemistry: Hydrolytic Enzymes.Amsterdam: Elsevier. pp. 39–158.
  6. ^Singleton A, Buttle DJ (January 2013). "Ficain".Handbook of Proteolytic Enzymes.Vol. 2: Metallopeptidases and Cysteine Peptidases. Academic Press. pp. 1877–9.doi:10.1016/B978-0-12-382219-2.00427-0.ISBN978-0-12-382219-2.
  7. ^ab"EC 3.4.22.3".IUBMB Enzyme Nomenclature.International Union of Biochemistry and Molecular Biology.Retrieved22 May2021.
  8. ^"Ficus insipidaWilld ".Plants of the World Online.Royal Botanic Gardens, Kew.Retrieved2020-10-09.
  9. ^abVatić S, Mirković N, Milošević JR, Jovčić B, Polović NĐ (December 2020). "Broad range of substrate specificities in papain and fig latex enzymes preparations improve enumeration of Listeria monocytogenes".International Journal of Food Microbiology.334(108851): 108851.doi:10.1016/j.ijfoodmicro.2020.108851.PMID32911158.
  10. ^Zare H, Moosavi-Movahedi AA, Salami M, Mirzaei M,Saboury AA,Sheibani N (March 2013)."Purification and autolysis of the ficin isoforms from fig (Ficus carica cv. Sabz) latex".Phytochemistry.87:16–22.Bibcode:2013PChem..87...16Z.doi:10.1016/j.phytochem.2012.12.006.PMC3755362.PMID23312458.
  11. ^Zaynoun ST, Aftimos BG, Abi Ali L, Tenek gian KK, Khalidi U, Kurban AK (July 1984). "Ficus carica; isolation and quantification of the photoactive components".Contact Dermatitis.11(1): 21–5.doi:10.1111/j.1600-0536.1984.tb00164.x.PMID6744838.Cited in McGovern and Barkley 2000, sectionPhytophotodermatitis.
  12. ^Ramezani R, Aminlari M, Fallahi H (July 2006). "Effect of Chemically Modified Soy Proteins and Ficin-tenderized Meat on the Quality Attributes of Sausage".Journal of Food Science.68(1): 85–88.doi:10.1111/j.1365-2621.2003.tb14119.x.
  13. ^Nishimura K, Higashiya K, Ueshima N, Kojima K, Takita T, Abe T, et al. (April 2021). "Insight into the collagen-degrading activity of a serine protease in the latex of Ficus carica cultivar Masui Dauphine".Bioscience, Biotechnology, and Biochemistry.85(5): 1147–1156.doi:10.1093/bbb/zbab025.PMID33580958.
  14. ^abHansson A, Zelada JC, Noriega HP (April 2005). "Reevaluation of risks with the use of Ficus insipida latex as a traditional anthelmintic remedy in the Amazon".Journal of Ethnopharmacology.98(3): 251–7.doi:10.1016/j.jep.2004.12.029.PMID15814256.
  15. ^"Clinical Aspects and Treatment of the More Common Intestinal Parasites of Man (TB-33)".Veterans Administration Technical Bulletin 1946 & 1947.10:1–14. 1948.
  16. ^The American Journal of Tropical Medicine.Williams and Wilkins. 1921. p. 377.
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