Genetic and other influences on red-cell flavin enzymes, pyridoxine phosphate oxidase and glutathione reductase in families with beta-thalassaemia.
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.
Anderson
B B
BB
Department of Haematology, St. Bartholomew's Hospital, London, U.K.
Perry
G M
GM
Clements
J E
JE
Studds
C
C
Fashola
R
R
Salsini
G
G
Vullo
C
C
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
D005182:Flavin-Adenine Dinucleotide; D009249:NADP; D011734:Pyridoxaminephosphate Oxidase; D000587:Oxidoreductases Acting on CH-NH Group Donors; D005980:Glutathione Reductase