flavin-adenine-dinucleotide and Glucosephosphate-Dehydrogenase-Deficiency

Red-cell studies were carried out on three groups of G6PD-deficient subjects with different G6PD variants from the Ferrara area of Northern Italy. Red-cell GSH and activities of G6PD, glutathione reductase (GR), glutathione peroxidase (GPx) and superoxide dismutase (SOD) were measured. A method was developed to measure red-cell GSH regeneration after oxidation of endogenous GSH in whole blood by diamide and only this clearly distinguished the variants from each other and from normal. Regeneration by 1 h was lowest in the Mediterranean variant, 0-10.2% in contrast to 93-98% in normal. A predisposition to a haemolytic crisis after ingestion of fava beans was not clearcut, but subjects appeared to be at risk if GSH regeneration at 1 h was less than 30% of the endogenous level, and red-cell FAD+ was very high indicated by high in vitro GR activity and inhibition by added FAD+. It is suggested that the most informative tests in G6PD deficiency are measurements of GSH regeneration in intact red cells plus GR activity and/or red-cell flavin compounds.

Topics: Adolescent; Adult; Erythrocytes; Female; Flavin-Adenine Dinucleotide; Glucosephosphate Dehydrogenase Deficiency; Glutathione; Glutathione Reductase; Humans; Male; Middle Aged

Per cent stimulation of GR activity by FAD in vitro and PNP oxidase activity were measured in G6PD deficiency, heterozygous beta-thalassaemia and controls. It is confirmed that, in contrast to the high stimulation of GR by FAD commonly found in in thalassaemia indicating red-cell deficiency of FAD, and shown here to be greater in the Italian subjects, GR is usually saturated with FAD in G6PD deficiency, leading to high in vitro activity. Unexpectedly, on the other hand, low FMN-dependent PNP oxidase activity due to red-cell deficiency of FMN, confirmed by response to oral riboflavin, was found in the majority of subjects with G6PD deficiency, similar to that found in heterozygous beta-thalassaemia. Whereas this is explained in thalassaemia by an inherited slow red-cell metabolism of riboflavin to FMN, it is suggested that in G6PD deficiency an increased rate of red-cell metabolism of FMN to FAD leads to the low FMN and high FAD. When G6PD deficiency occurs with heterozygous beta-thalassaemia, GR is usually saturated with FAD as in G6PD deficiency alone, unless there is an inherited, very slow red-cell metabolism of riboflavin to FMN. The part played by GR in haemolytic crises in G6PD deficiency is discussed.

Topics: Erythrocytes; Flavin Mononucleotide; Flavin-Adenine Dinucleotide; Flavoproteins; Glucosephosphate Dehydrogenase Deficiency; Glutathione Reductase; Heterozygote; Humans; Oxidoreductases Acting on CH-NH Group Donors; Pedigree; Pyridoxal Phosphate; Pyridoxaminephosphate Oxidase; Riboflavin; Thalassemia

Erythrocyte NAD(P)H2 glutathione oxidoreductase (EC 1.6.4.2.) activation coefficients (EGR AC) and D-glucose-6-phosphate: NADP 1-oxidoreductase, EC 1.1.1.49 (G-6-PD) activities were measured in 155 West African women to determine whether heterozygous G-6-PD deficiency produces false negative results in the EGR test for riboflavin deficiency. A positive correlation was found between EGR AC and G-6-PD activity demonstrating that heterozygous G-6-PD deficiency does result in abnormally depressed EGR AC values when G-6-PD activity is significantly reduced. However, heterozygous deficient genotypes with normal G-6-PD activity showed undepressed EGR AC values. These results indicate that, in its present form, the EGR test is not a suitable index of riboflavin status in subjects whose G-6-PD activity is less than 9 IU/g Hb when measured by the WHO-37 degrees assay.

Topics: Adult; Clinical Enzyme Tests; Enzyme Activation; Erythrocytes; False Negative Reactions; Female; Flavin-Adenine Dinucleotide; Genotype; Glucosephosphate Dehydrogenase; Glucosephosphate Dehydrogenase Deficiency; Glutathione Reductase; Heterozygote; Humans; Riboflavin Deficiency

Topics: Ascorbic Acid; Blood; Carbon Radioisotopes; Enzyme Activation; Erythrocytes; Flavin-Adenine Dinucleotide; Flavins; Glucosephosphate Dehydrogenase Deficiency; Glutathione Reductase; Hemolysis; Humans; Liver Cirrhosis; Methylene Blue; Riboflavin; Umbilical Cord; Uremia

Topics: Catalase; Cholinesterases; Clinical Enzyme Tests; Erythrocytes; Flavin-Adenine Dinucleotide; Galactosemias; Glucosephosphate Dehydrogenase Deficiency; Glutathione Reductase; Humans; L-Lactate Dehydrogenase; Lesch-Nyhan Syndrome; Metabolism, Inborn Errors; NAD; NADP; Nicotinic Acids; Pyridoxine; Riboflavin

Topics: Adult; Erythrocytes; Flavin-Adenine Dinucleotide; Glucosephosphate Dehydrogenase Deficiency; Glutathione Reductase; Humans; Liver Cirrhosis; Protein Binding; Uremia

Topics: Anemia, Aplastic; Erythrocytes; Family; Flavin-Adenine Dinucleotide; Genetics, Medical; Glucosephosphate Dehydrogenase Deficiency; Glutathione Reductase; Hemolysis; Humans; Male; Riboflavin; Riboflavin Deficiency; Stimulation, Chemical; Thailand

Topics: Acetylcholinesterase; Adenosine Triphosphate; Enzyme Activation; Enzyme Repression; Erythrocytes; Flavin-Adenine Dinucleotide; Glucosephosphate Dehydrogenase Deficiency; Glutathione; Glutathione Reductase; Hemolysis; Humans; Metabolism, Inborn Errors; Pyruvate Kinase

Topics: Environment; Erythrocytes; Flavin-Adenine Dinucleotide; Glucosephosphate Dehydrogenase Deficiency; Glutathione Reductase; Humans; Protein Binding

Topics: Adult; Erythrocytes; Erythrocytes, Abnormal; Flavin-Adenine Dinucleotide; Glucosephosphate Dehydrogenase; Glucosephosphate Dehydrogenase Deficiency; Glutathione Reductase; Humans; Male