Ficain

Ficain
Crystallographic structure of ficain from Ficus carica, rainbow colored, N-terminus blue, C-terminus red.
Identifiers
EC no.	3.4.22.3
CAS no.	9001-33-6
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Search PMC articles PubMed articles NCBI proteins

Ficain also known as ficin, debricin, or higueroxyl delabarre (EC 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.^[1][2][3][4]

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.^[5] 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.^[5]

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.^[6] 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.^[7] 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,^[2] a taxon which has since been synonymised with F. 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

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.^[2] Purified ficin is not actually 'pure', it is a mix of different enzymes and can be produced from many different species of Ficus.^[2] A commonly used ficin is made from the latex of the common fig and 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 different cultivars of common fig contain different ratios of these enzymes.^[10] 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.^[11] 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,^[2][3] 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,^[3] and for unmasking antigens in serology.^[2] 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.^[5]

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.^[3] 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.^[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 from Ficus carica also appears to contain an enzyme which shows marked ability to digest collagen, as opposed to papain.^[9] This, however, is not a cysteine protease, but a serine protease.^[13]

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).^[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 as leche de higuerón, and it was considered to be the most effective treatment for trichuriasis at the time.^[15] Species used in the production of leche de higuerón in the 1920s included F. glaborata and F. laurifolia.^[16]

References

1. "ENZYME 3.4.22.3 ficain". Expasy - Swiss Bioinformatics Resource Portal. Swiss Institute of Bioinformatics. Retrieved 22 May 2021.
2. Arribére MP, Caffin O, Priolo S (2000). "Proteolytic Enzymes from the Latex of Ficus pumila L. (Moraceae)" (PDF). Acta Farmacéutica Bonaerense. 19 (4): 257–262. Retrieved 22 May 2021.
3. "Ficin". Vitamins & Supplements. WebMD LLC. 2021. Retrieved 22 May 2021.
4. Liener IE, Friedenson B (1970). Ficin. Methods Enzymol. Vol. 19. pp. 261–273. doi:10.1016/0076-6879(70)19020-3. ISBN 978-0-12-181881-4.
5. Brocklehurst 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. ISBN 978-0-12-382219-2.
7. "EC 3.4.22.3". IUBMB Enzyme Nomenclature. International Union of Biochemistry and Molecular Biology. Retrieved 22 May 2021.
8. "Ficus insipida Willd". Plants of the World Online. Royal Botanic Gardens, Kew. Retrieved 2020-10-09.
9. Vatić 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. PMID 32911158.
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. PMC 3755362. PMID 23312458.
11. Zaynoun ST, Aftimos BG, Abi Ali L, Tenekjian 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. PMID 6744838. Cited in McGovern and Barkley 2000, section Phytophotodermatitis.
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. PMID 33580958.
14. Hansson 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. PMID 15814256.
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.

External links

• Ficain at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• EC 3.4.22.3