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Mechanisms of red cell clearance in favism.

Divicine (2,6-diamino-4,5-dihydroxypyrimidine) is a quinoid compound contained in high amounts in all fava bean strains. It elicits a number of metabolic and rheological modifications in G6PD-deficient RBC. Besides this, it stimulates erythrophagocytosis by mouse peritoneal macrophages and formation of crossbonded red cells. The latter are intracellularly membrane-bonded red cells, which form during hypertonic incubation and subsequent swelling. All effects observed in vitro were also observed in vivo in the early phases of fabic hemolysis. In particular, phagocytosis and crossbonding offer a basis for understanding extravasal hemolysis.

Animals↗

Effect of divicine and isouramil on red cell metabolism in normal and G6PD-deficient (Mediterranean variant) subjects. Possible role in the genesis of favism.

Fava beans contain high amounts (up to 6.7 g/100 g dry weight) vicine and convicine. Their active aglycones divicine and isouramil have equivalent metabolic effects. They rapidly oxidize GSH to GSSG in normal and G6PD-deficient red cells. No regeneration of GSH occurs in deficient cells. The stoichiometry of the divicine oxidation of GSH is 1:1. Ascorbic acid is quickly oxidized by isouramil in both normal and deficient cells but regenerates only in normal cells. Isouramil oxidizes NADH at a much lesser extent than NADPH. Glycolysis is activated at the glyceraldehyde 3-phosphate dehydrogenase step. Divicine strongly stimulates hexone monophosphate shunt only in normal red cells. Divicine alone or associated with ascorbic acid has almost no effect in deficient red cells. Malonyl dialdehyde production is slight and virtually the same in normal and deficient cells treated with 5 mM isouramil. Large polypeptide aggregates are formed after 12 and 24 hours incubation with 1 mM divicine in deficient cells only. Divicine (0.25 mM) markedly decreases the filterability of deficient cells. The results are consistent with a causal role of divicine/isouramil in the genesis of the hemolytic crisis occurring in G6PD-deficient subjects after fava bean ingestion.

Ascorbic Acid↗

[Genetic improvement in Vicia faba and favism. I. Distribution and levels of presumably hemolytic metabolites].

Covicine + vicine, L-DOPA-glucoside + L-DOPA and ascorbic acid were determined in different lines of Vicia faba beans throughout the biological cycle of the plant. As the seed matures the levels of convicine + vicine as well as of ascorbic acid decrease with seed maturation in all the lines examined. L-DOPA, which is lacking in cotyledons but present in the tegument, also decrease and is nearly undectable in some lines with white flowers.

Ascorbic Acid↗

[Genetic improvement in Vicia and favism. II. Glycosidase activity].

Glycosidase activities with starch and PNP-glycosides as substrates can be detected in the cotyledons, leaves, pods and teguments of Vicia faba beans. The mainly hydrolize alpha- and beta-glucosides, alpha- and beta-galactosides as well as starch. The amylase activity arises at very early stages of seed maturation and then rapidly decreases, whereas glycosidases increase up to the 30% of the beans dry weight before decreasing. The beta-glucosidase might play a role in regulating the metabolism of possibly haemolitic glycosides (i.e. vicine, convicine and L-DOPA glucoside) thus explaining the presence of this enzyme.

Fabaceae↗