An association between favism (a hemolytic reaction to consumption of fava beans), glucose-6-phosphate dehydrogenase deficiency (G6PD-) and acid phosphatase locus 1 (ACP1) phenotypes has been reported; the frequency of carriers of the pa and pc ACP1 alleles was found to be significantly higher in G6PD- individuals showing favism than in the general population. Here, we investigated the hypothesis that favism is caused by toxic Vicia faba substances, which in some ACP1 phenotypes cause increased phosphorylation and consequently increased glycolysis, with strong reduction in reduced glutathione production, resulting in hemolysis. It has been demonstrated that ACP1 f isoforms have physiological functions different from those of s isoforms and are responsible for most of the phosphatase activity, in addition to being less stable in the presence of oxidizing molecules. Thus, the C, CA and A phenotypes, characterized by lower concentrations of f isoforms, could be more susceptible to damage by oxidative events compared to the other phenotypes. To test this hypothesis, the (f+s) enzymatic activity of different ACP1 phenotypes with and without added V. faba extract was analyzed. Enzymatic activities of ACP1 A, -CA, -C groups (low activity) and -B, -BA, -CB groups (high activity) were significantly different after addition of V. faba extract. Phenotypes A, CA and C had extremely low enzymatic activity levels, which would lead to low levels of reduced glutathione and bring about erythrocyte lysis.
Association between ACP(1) genetic polymorphism and favism.
POLZONETTI, Valeria;PASSINI, Valerio;LUCARINI, Nazzareno
2011-01-01
Abstract
An association between favism (a hemolytic reaction to consumption of fava beans), glucose-6-phosphate dehydrogenase deficiency (G6PD-) and acid phosphatase locus 1 (ACP1) phenotypes has been reported; the frequency of carriers of the pa and pc ACP1 alleles was found to be significantly higher in G6PD- individuals showing favism than in the general population. Here, we investigated the hypothesis that favism is caused by toxic Vicia faba substances, which in some ACP1 phenotypes cause increased phosphorylation and consequently increased glycolysis, with strong reduction in reduced glutathione production, resulting in hemolysis. It has been demonstrated that ACP1 f isoforms have physiological functions different from those of s isoforms and are responsible for most of the phosphatase activity, in addition to being less stable in the presence of oxidizing molecules. Thus, the C, CA and A phenotypes, characterized by lower concentrations of f isoforms, could be more susceptible to damage by oxidative events compared to the other phenotypes. To test this hypothesis, the (f+s) enzymatic activity of different ACP1 phenotypes with and without added V. faba extract was analyzed. Enzymatic activities of ACP1 A, -CA, -C groups (low activity) and -B, -BA, -CB groups (high activity) were significantly different after addition of V. faba extract. Phenotypes A, CA and C had extremely low enzymatic activity levels, which would lead to low levels of reduced glutathione and bring about erythrocyte lysis.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
