Further evidence for heterogeneity of glucose-6-phosphate dehydrogenase deficiency in Papua New Guinea

Summary Four new G6PD variants have been characterized in individuals from Papua New Guinea. This study demonstrates that the previously reported Markham variant and the newly characterized Salata variant may be widely distributed in Papua New Guinea. The data presented here together with those of previously published studies demonstrate a degree of heterogeneity of G6PD deficiency that is much higher than that in other regions of the world where G6PD deficiency is common.     

Glucose-6-phosphate dehydrogenase deficiency in Papua New Guinea

Summary A total of 362 males from various regions of Papua New Guinea were screened for red cell glucose-6-phosphate dehydrogenase (G6PD) activity. Twenty-six G6PD deficient individuals were identified. Biochemical characterization of G6PD purified from these subjects has revealed 13 new variants and several copies of previously described forms of G6PD. This study illustrates the extreme heterogeneity of G6PD deficiency among the people of Papua New Guinea.     

Kinetics of human erythrocyte glucose-6-phosphate dehydrogenase dimers

The steady-state kinetics of human erythrocyte glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate: NADP+ 1-oxidoreductase, EC 1.1.1.49) dimers were studied by initial rate measurement. These experiments gave intersecting double-reciprocal plots suggesting a ternary complex mechanism with a Km for NADP and glucose 6-phosphate of 11 microM and 43 microM, respectively. These studies were combined with rate measurements in the presence of one product (NADPH), dead-end inhibitors, as well as alternative substrates. The inhibition by NADPH was found to be competitive with respect to both substrates. Alternate substrates experiments gave linear double-reciprocal plots over a wide range of substrate concentrations. The results suggest that the dimeric enzyme follows either a random or a Theorell-Chance mechanism.     

Sigmoid kinetics of human erythrocyte glucose-6-phosphate dehydrogenase

Several disagreements and inconsistencies have appeared regarding whether human erythrocyte glucose-6-phosphate dehydrogenase exhibits sigmoid or classical kinetics with respect to NADP+ binding. The latest report is that the purified enzyme exhibits classical kinetics while the intracellular enzyme exhibits sigmoid kinetics (H. N. Kirkman, and G. F. Gaetani (1986) J. Biol. Chem. 261, 4033-4038). The various investigations were carried out at fixed pH, ionic strength, and temperature. The steady-state kinetics of crude and purified erythrocyte glucose-6-phosphate dehydrogenase are reported here at various temperatures, ionic strengths, and pH values and as a function of glucose 6-phosphate concentration. Sigmoid kinetics were observed for both purified and crude enzyme samples at high pH, temperature, ionic strength, and concentration of glucose 6-phosphate with Hill coefficients varying between 1.40 and 1.90. In contrast, at low pH, temperature, and ionic strength, the crude enzyme samples exhibit sigmoid kinetics while the purified samples exhibit classical kinetics despite the high concentration of glucose 6-phosphate. High concentrations of glucose 6-phosphate and factors favoring the enzyme in the dimeric form are necessary conditions for the observation of sigmoid kinetics in human erythrocyte glucose-6-phosphate dehydrogenase. These factors are high pH, ionic strength, and temperature. The observed sigmoid kinetics in this enzyme is explained as arising from tetramer-dimer transitions.     

Heterogeneity of glucose-6-phosphate dehydrogenase deficiency in Algeria

Summary Glucose-6-phosphate dehydrogenase (G6PD) deficiency was found in 3.2% of the male population living in the urban area of Algiers. The deficient subjects originated from multiple geographic regions of Northern Algeria, with prevalence of individuals of Berber-Kabyle origin. Red blood cell G6PD was partially purified and characterized in deficient males from 17 families, and six different variants were found. Among them, only one, the Gd(-) Kabyle variant, had been previously described. It was detected in nine families. The other five variants were new: Gd(-) Laghouat (four cases), Gd(-) Blida (one case), Gd(-) Thenia (one case), Gd(-) Titteri (one case), and Gd(-) Alger (two brothers), Strikingly, the common Mediterranean variant was not found. G6PD deficiency is heterogeneous in northern Algeria where autochtonous variants seem to prevail. The Kabyle variant may be common in this country.     

Drug-induced haemolysis in glucose-6-phosphate dehydrogenase deficiency.

People with the variants of glucose-6-phosphate dehydrogenase (GPD) deficiency common in the southern Chinese (Canton, B(-)Chinese, and Hong Kong-Pokfulam) have a moderate shortening of red-cell survival but no anaemia when they are in the steady state. With a cross-transfusion technique, primaquine, nitrofurantoin, and large doses of aspirin were found to aggravate the haemolysis while sulphamethoxazole did so only in some people. Individual differences in drug metabolism may be the reason for this. Many commonly used drugs reported to accentuate haemolysis in GPD deficiency did not shorten red-cell survival.     

Cortisol levels in glucose-6-phosphate dehydrogenase deficiency.

The aim of the present study was to investigate cortisol levels under basal conditions and in response to ACTH stimulation in male patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. The study included 14 male controls and 12 patients with G-6-PD deficiency matched for age and race. Fasting blood samples were taken from all the subjects at rest, and 30, 60 and 120 min after the infusion of 0.25 mg of corticotropin for cortisol determination. The mean cortisol levels observed in the first hour after ACTH stimulation in the G-6-PD-deficient patients were significantly (p = 0.03) lower than in the control group. No significant differences were observed between patients and controls at rest, and in the second hour after stimulation. These data suggest that, in the adrenals, G-6-PD plays a role in the initial phase of cortisol production. However, 1 h after ACTH stimulation, G-6-PD probably is no longer rate limiting in the production of cortisol.