:Vicine

Vicine was initially isolated in 1870 from the seeds of Vicia sativa by a method of extraction with sulfuric acid and subsequent precipitation with mercury sulfate (HgSO₄). Later vicine was also found in other Vicia species, namely Vicia faba, beet juice and peas. The chemical structure of the compound was built gradually. First the glycosidic nature of the compound was recognized in 1896. The same year the aglycone of vicine, divicine, was isolated. In the beginning of the 20th century the pyrimidine structure was recognized. Despite these initial successes, the correct formula of vicine was determined only in 1953 and it is 2,4-diamino-6-oxypyrimidine-5-(β-D-glucopyranoside).

Vicine is an inactive compound in the body. When vicine enters the body through food, it is hydrolysed by intestinal microflora to the highly reactive free radical generating aglycone divicine. Upon hydrolysis, the glucose part of the molecule is split off and that results in the reduced divicine. Divicine is then taken up in the blood through the intestinal epithelium.{{cite journal|vauthors=Baker MA, Bosia A, Pescarmona G, Turrini F, Arese P |title=Mechanism of action of divicine in a cell-free system and in glucose-6-phosphate dehydrogenase-deficient red cells |journal=Toxicologic Pathology |volume=12 |issue=4 |pages=331–6 |date=June 1984 |pmid=6099911 |doi=10.1177/019262338401200405 |s2cid=26038580}}{{cite journal|vauthors=Luzzatto L, Arese P |title=Favism and Glucose-6-Phosphate Dehydrogenase Deficiency |journal=The New England Journal of Medicine |volume=378 |issue=1 |pages=60–71 |date=January 2018 |pmid=29298156 |doi=10.1056/NEJMra1708111}}

Adverse effects almost solely occur in humans that suffer from glucose-6-phosphate dehydrogenase deficiency. This deficiency causes a shortage of glutathione in erythrocytes and glutathione is needed for the neutralization of ROS (reactive oxygen species) created by the strongly oxidizing agent divicine. Glucose-6-phosphate dehydrogenase deficiency is a common genetic condition, with a global prevalence of approximately 4.9%, affecting over 400 million individuals worldwide.{{Cite journal |last1=Khazaei |first1=Hamid |last2=Purves |first2=Randy W. |last3=Hughes |first3=Jessa |last4=Link |first4=Wolfgang |last5=O'Sullivan |first5=Donal M. |last6=Schulman |first6=Alan H. |last7=Björnsdotter |first7=Emilie |last8=Geu-Flores |first8=Fernando |last9=Nadzieja |first9=Marcin |last10=Andersen |first10=Stig U. |last11=Stougaard |first11=Jens |last12=Vandenberg |first12=Albert |last13=Stoddard |first13=Frederick L. |date=2019-09-01 |title=Eliminating vicine and convicine, the main anti-nutritional factors restricting faba bean usage |journal=Trends in Food Science & Technology |volume=91 |pages=549–556 |doi=10.1016/j.tifs.2019.07.051 |issn=0924-2244|doi-access=free }} It is important to recognize that glucose-6-phosphate dehydrogenase deficiency can still be life-threatening if not promptly diagnosed and managed. Effective management often includes interventions as blood transfusions, but with appropriate care, full recovery from favism without lasting complications is the expected outcome.{{Cite journal |last1=Reading |first1=N. Scott |last2=Sirdah |first2=Mahmoud M. |last3=Shubair |first3=Mohammad E. |author3-link=Mohammed Shabir |last4=Nelson |first4=Benjamin E. |last5=Al-Kahlout |first5=Mustafa S. |last6=Al-Tayeb |first6=Jamal M. |last7=Aboud |first7=Lina N. |last8=Shaban |first8=Maysaa Abu |last9=Luzzatto |first9=Lucio |last10=Prchal |first10=Josef T. |date=2016-09-01 |title=Favism, the commonest form of severe hemolytic anemia in Palestinian children, varies in severity with three different variants of G6PD deficiency within the same community |url=https://www.sciencedirect.com/science/article/pii/S1079979616300821 |journal=Blood Cells, Molecules and Diseases |volume=60 |pages=58–64 |doi=10.1016/j.bcmd.2016.07.001 |pmid=27519946 |issn=1079-9796|url-access=subscription }}

Persons with G6PD deficiency are asymptomatic. An attack of acute haemolytic anaemia can appear out of nowhere and can be very severe and life-threatening. Indications of such a sudden attack of favism are dark urine, pallor, jaundice, abdominal pain and in most cases fever.

The β-glycosidic bond between glucose and the hydroxyl group at C5 on the pyrimidine ring are hydrolysed to yield the aglycone of vicine, divicine (2,6-diamino-4,5-dihydroxypyrimidine).{{cite journal|vauthors=Rizzello CG, Losito I, Facchini L, Katina K, Palmisano F, Gobbetti M, Coda R |title=Degradation of vicine, convicine and their aglycones during fermentation of faba bean flour |journal=Scientific Reports |volume=6 |issue=1 |pages=32452 |date=August 2016 |pmid=27578427 |pmc=5006014 |doi=10.1038/srep32452 |bibcode=2016NatSR...632452R}} These aglycones have a strong oxidising capacity for glutathione.{{cite journal|vauthors=Mager J, Glaser G, Razin A, Izak G, Bien S, Noam M |title=Metabolic effects of pyrimidines derived from fava bean glycosides on human erythrocytes deficient in glucose-6-phosphate dehydrogenase |journal=Biochemical and Biophysical Research Communications |volume=20 |issue=2 |pages=235–40 |date=July 1965 |pmid=5850686 |doi=10.1016/0006-291x(65)90352-9}} In healthy individuals, this is not a problem, as glutathione can be reduced quickly enough to regenerate it. In individuals with a deficiency for glucose 6-phosphate dehydrogenase (G6PD) however, this results in haemolytic anaemia.{{cite journal|vauthors=Pulkkinen M, Zhou X, Lampi AM, Piironen V |title=Determination and stability of divicine and isouramil produced by enzymatic hydrolysis of vicine and convicine of faba bean |journal=Food Chemistry |volume=212 |pages=10–9 |date=December 2016 |pmid=27374500 |doi=10.1016/j.foodchem.2016.05.077}}

A 10 g vicine /kg diet in laying hens led to reduced feed intake, egg weight, haemoglobin levels and fertility and increased liver weights, liver glutathione levels and plasma lipid levels. A diet with comparable levels of vicine per kg in pigs showed only small effects on protein and energy digestibility.{{Cite journal|vauthors=Jezierny D, Mosenthin R, Bauer E |date=May 2010 |title=The use of grain legumes as a protein source in pig nutrition: A review |journal=Animal Feed Science and Technology |volume=157|issue=3–4|pages=111–128|doi=10.1016/j.anifeedsci.2010.03.001}}

In another study, laying and broiler hens were fed grains that were soaked for different periods of time, which partly or totally removed vicine. Hens that had had grains with vicine still in them showed a significant decrease in corpuscular haemoglobin, while the others did not.{{cite journal|vauthors=Farran MT, Darwish AH, Uwayjan MG, Sleiman FT, Ashkarian VM |title=Vicine and convicine in common vetch (Vicia sativa) seeds enhance beta-cyanoalanine toxicity in male broiler chicks |journal=International Journal of Toxicology |volume=21 |issue=3 |pages=201–9 |date=June 2002 |pmid=12055021 |doi=10.1080/10915810290096333 |s2cid=21101425}}

An in vivo study in rats showed that oral administration of vicine resulted in only small reductions in glutathione concentrations and no mortality. Intraperitoneal administration however, led to a rapid decrease in glutathione followed by death because of anoxia.{{cite journal|vauthors=Arbid MS, Koriem KM, Asaad GF, Megahed HA |title=Effect of the antibiotic neomycin on the toxicity of the glycoside vicine in rats |journal=Journal of Toxicology |volume=2013 |pages=913128 |date=2013 |pmid=23840205 |pmc=3694484 |doi=10.1155/2013/913128 |doi-access=free}}

{{reflist|30em}}

• {{Commons category-inline}}
• [http://www.ansci.cornell.edu/plants/toxicagents/vicine.html Cornell University page on vicine]

{{Glycosides}}

Category:Alkaloid glycosides

Category:Pyrimidones

Category:Alkaloids found in Fabaceae

Category:Plant toxins