title: Genetic and other influences on red-cell flavin enzymes, pyridoxine phosphate oxidase and glutathione reductase in families with beta-thalassaemia.
abstract: In 18 beta-thalassaemia families from the Ferrara area the incidence of an inherited low flavin mononucleotide (FMN)-dependent pyridoxine phosphate (PNP) oxidase activity, a sensitive indicator of red-cell FMN deficiency, is higher in related members in these families than in the unrelated spouses and controls subjects without family history of thalassaemia. This suggests slower red-cell riboflavin metabolism in thalassaemia families, which may have resulted from selection in combination with thalassaemia by malaria. However, there was a markedly higher incidence of red-cell flavin adenine dinucleotide (FAD) deficiency in thalassaemia heterozygotes than in their normal relatives. This was indicated by higher stimulation of FAD-dependent glutathione reductase (GR) activity by FAD and lower GR activity per red cell, and suggests a marked additive effect by thalassaemia on the red cell FAD deficiency that results from the inherited slow riboflavin metabolism. There is evidence that diversion of FAD to other FAD-dependent enzymes might be an important factor.
authors.affiliation: Department of Haematology, St. Bartholomew's Hospital, London, U.K.
authors.forename: B B
authors.initials: BB
authors.lastname: Anderson
authors.forename: G M
authors.initials: GM
authors.lastname: Perry
authors.forename: J E
authors.initials: JE
authors.lastname: Clements
authors.forename: C
authors.initials: C
authors.lastname: Studds
authors.forename: R
authors.initials: R
authors.lastname: Fashola
authors.forename: G
authors.initials: G
authors.lastname: Salsini
authors.forename: C
authors.initials: C
authors.lastname: Vullo
mesh_terms: D000328:Adult; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology*; D005182:Flavin-Adenine Dinucleotide / Q000494:pharmacology; D005980:Glutathione Reductase / Q000097:blood*; D006579:Heterozygote; D006801:Humans; D007700:Kinetics; D008875:Middle Aged; D009249:NADP / Q000097:blood; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000097:blood*; D011734:Pyridoxaminephosphate Oxidase / Q000097:blood*; D013789:Thalassemia / Q000201:enzymology* / Q000235:genetics
chemical_list: D005182:Flavin-Adenine Dinucleotide; D009249:NADP; D011734:Pyridoxaminephosphate Oxidase; D000587:Oxidoreductases Acting on CH-NH Group Donors; D005980:Glutathione Reductase