Divicine
Encyclopedia
Divicine is an oxidant and a base with alkaloidal properties found in fava beans and Lathyrus sativus
. It is an aglycone
of vicine
. A common derivative is the diacetate form (2,6-diamino-1,6-dihydro-4,5-pyrimidinedione).
, also known as khesari, which is a cheap and robust food source commonly grown in Asia and East Africa.
.
A simplified three-step process for artificial divicine synthesis: (1) The benzyl group of 2-amino-5-benzyloxy-4-hydroxypyrimidine is removed by acid hydrolysis
, yielding 2-amino-4,5-dihydroxypyrimidine. (2) This intermediate is then treated with nitrous acid to yield the slightly soluble orange product, 2-amino-6-nitrosopyrimidine-4,5-diol (3) which is then reduced with sodium dithionite
to yield divicine.
(G6PD or G6PDH) deficiency. This deficiency, an X-linked recessive hereditary disease, is the most common enzyme deficiency worldwide. It is particularly common in those of African, Asian, Mediterranean, and Middle-Eastern descent. Symptoms of favism include hemolysis
, prolonged jaundice
, kernicterus
, and even acute renal failure
in extreme cases.
The specific mechanism of divicine’s toxicity is still unknown. It had been established that the β–glucosides vicine
and convicine were linked to the precipitation of hemolytic crises in G6PDH-deficient individuals, but in a more recent study of rat erythrocyte toxicity, exposure to 1.5 mM of divicine dramatically reduced survival rates while exposure to 5 mM of vicine
did not. These results suggest that divicine is a direct-acting hemolytic agent and likely the direct cause of favism.
Divicine is also present in and at least partially responsible for the poisonous action of Lathyrus sativus
- a legume commonly grown in drought- and famine-prone regions of Asia and East Africa as an ‘insurance crop’ for human consumption and livestock feed when other crops fail to grow, despite their known health hazards.
Lathyrus sativus
Lathyrus sativus, is a legume commonly grown for human consumption and livestock feed in Asia and East Africa. It is a particularly important crop in areas that are prone to drought and famine, and is thought of as an 'insurance crop' as it produces reliable yields when all other crops...
. It is an aglycone
Aglycone
An aglycone is the non-sugar compound remaining after replacement of the glycosyl group from a glycoside by a hydrogen atom. The spelling aglycon is sometimes encountered .Classes of phytochemicals found in the aglycone and glycosides forms :...
of vicine
Vicine
Vicine is an alkaloid glycoside found in fava beans. Vicine is toxic, causing the disease favism, in individuals who have a hereditary loss of the enzyme glucose-6-phosphate dehydrogenase,-External links:*...
. A common derivative is the diacetate form (2,6-diamino-1,6-dihydro-4,5-pyrimidinedione).
Occurrence
Divicine is found in fava beans and in the legume Lathyrus sativusLathyrus sativus
Lathyrus sativus, is a legume commonly grown for human consumption and livestock feed in Asia and East Africa. It is a particularly important crop in areas that are prone to drought and famine, and is thought of as an 'insurance crop' as it produces reliable yields when all other crops...
, also known as khesari, which is a cheap and robust food source commonly grown in Asia and East Africa.
Synthesis
In plants, reduced divicine is formed from the hydrolysis of the inactive β–glucoside, vicineVicine
Vicine is an alkaloid glycoside found in fava beans. Vicine is toxic, causing the disease favism, in individuals who have a hereditary loss of the enzyme glucose-6-phosphate dehydrogenase,-External links:*...
.
A simplified three-step process for artificial divicine synthesis: (1) The benzyl group of 2-amino-5-benzyloxy-4-hydroxypyrimidine is removed by acid hydrolysis
Acid hydrolysis
Acid hydrolysis is a chemical process in which acid is used to convert cellulose or starch to sugar.It implies a chemical mechanism of hydrolysis catalyzed by a Brønsted-Lowry or Arrhenius acid. By contrast, it does not usually imply hydrolysis by direct electrophilic attack—as may originate from...
, yielding 2-amino-4,5-dihydroxypyrimidine. (2) This intermediate is then treated with nitrous acid to yield the slightly soluble orange product, 2-amino-6-nitrosopyrimidine-4,5-diol (3) which is then reduced with sodium dithionite
Sodium dithionite
Sodium dithionite is a white crystalline powder with a weak sulfurous odor. It is a sodium salt of dithionous acid. Although it is stable under most conditions, it will decompose in hot water and in acid solutions...
to yield divicine.
Toxicity
Divicine has been deemed a hemotoxic component of fava beans and plays a role in the development of favism, a disorder that involves a hemolytic response to the consumption of broad beans due to glucose-6-phosphate dehydrogenaseGlucose-6-phosphate dehydrogenase
Glucose-6-phosphate dehydrogenase is a cytosolic enzyme in the pentose phosphate pathway , a metabolic pathway that supplies reducing energy to cells by maintaining the level of the co-enzyme nicotinamide adenine dinucleotide phosphate...
(G6PD or G6PDH) deficiency. This deficiency, an X-linked recessive hereditary disease, is the most common enzyme deficiency worldwide. It is particularly common in those of African, Asian, Mediterranean, and Middle-Eastern descent. Symptoms of favism include hemolysis
Hemolysis
Hemolysis —from the Greek meaning "blood" and meaning a "loosing", "setting free" or "releasing"—is the rupturing of erythrocytes and the release of their contents into surrounding fluid...
, prolonged jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
, kernicterus
Kernicterus
Kernicterus is damage to the brain centers of infants caused by increased levels of unconjugated bilirubin. This may be due to several underlying pathologic processes. Newborn babies are often polycythemic. When they break down the erythrocytes, one of the byproducts is bilirubin, which circulates...
, and even acute renal failure
Acute renal failure
Acute kidney injury , previously called acute renal failure , is a rapid loss of kidney function. Its causes are numerous and include low blood volume from any cause, exposure to substances harmful to the kidney, and obstruction of the urinary tract...
in extreme cases.
The specific mechanism of divicine’s toxicity is still unknown. It had been established that the β–glucosides vicine
Vicine
Vicine is an alkaloid glycoside found in fava beans. Vicine is toxic, causing the disease favism, in individuals who have a hereditary loss of the enzyme glucose-6-phosphate dehydrogenase,-External links:*...
and convicine were linked to the precipitation of hemolytic crises in G6PDH-deficient individuals, but in a more recent study of rat erythrocyte toxicity, exposure to 1.5 mM of divicine dramatically reduced survival rates while exposure to 5 mM of vicine
Vicine
Vicine is an alkaloid glycoside found in fava beans. Vicine is toxic, causing the disease favism, in individuals who have a hereditary loss of the enzyme glucose-6-phosphate dehydrogenase,-External links:*...
did not. These results suggest that divicine is a direct-acting hemolytic agent and likely the direct cause of favism.
Divicine is also present in and at least partially responsible for the poisonous action of Lathyrus sativus
Lathyrus sativus
Lathyrus sativus, is a legume commonly grown for human consumption and livestock feed in Asia and East Africa. It is a particularly important crop in areas that are prone to drought and famine, and is thought of as an 'insurance crop' as it produces reliable yields when all other crops...
- a legume commonly grown in drought- and famine-prone regions of Asia and East Africa as an ‘insurance crop’ for human consumption and livestock feed when other crops fail to grow, despite their known health hazards.