GLUCOSE-6-PHOSPHATE dehydrogenase (G6PD) Deficiency is the most prevalent enzymopathy in mankind. It has sex-linked inheritance. This enzyme exists in all cells. G6PD deficiency increases the sensitivity of red blood cells to oxidative damage. G6PD deficiency was discovered in 1950 when some people suffered hemolytic anemia as a result of taking antimalarial drugs (primaquin). Most people with G6PD deficiency do not have any symptoms, till they are exposed to certain medications, Fava beans and infections; and then their red blood cells are hemolyzed. The degree of hemolysis changes according to the degree of enzyme deficiency and the oxidant agent exposure. G6PD deficiency has many different variants and Mediterranean variant is the most common mutation in the world. G6PD deficiency is considered a health problem worldwide, especially in Asia, Middle East and Mediterranean countries. In this article, we have reviewed the importance and function of G6PD enzyme, incidence rate of G6PD deficiency in the world and Iran, genetic and variants of this enzyme, clinical manifestation, diagnosis and treatment of the enzyme deficiency.

Background: Jaundice is affecting over 60-80 percent of neonates in the first week of life. GLUCOSE-6-PHOSPHATE dehydrogenase (G6PD) deficiency, which is an important cause of pathologic hyperbilirubinemia, can lead to hemolytic anemia, jaundice and kernicterus. The present study was performed to determine the prevalence of G6PD deficiency among icteric neonates in Shirvan, Iran.Methods: This descriptive, analytical study was performed by evaluating the medical records of neonates with jaundice, admitted to the neonatal ward of Imam Khomeini Hospital of Shirvan in 2012-2013. All neonates, who were evaluated in terms of G6PD, were included in this study. Data including the clinical signs and symptoms, laboratory test results and maternal history during pregnancy were recorded in the questionnaires. The patients were divided into two groups: with and without G6PD deficiency. The recorded data were compared between the two groups, using t-test and Chi-square test. P-value less than 0.05 was considered statistically significant.Results: Among 452 admitted neonates, 16 (3.5%) presented with G6PD deficiency. There was no significant difference between the two groups in terms of birth weight, weight on admission, Coombs’ test results, hematocrit level, length of hospital stay and total bilirubin level. However, there was a significant difference between the two groups regarding reticulocyte count.Conclusion: Based on the findings, establishment of an early G6PD screening program, which can prevent further complications in neonates, seems essential, particularly in countries such as Iran where G6PD deficiency is highly prevalent.

Background: GLUCOSE 6-PHOSPHATE dehydrogenase (G6PD), the first enzyme in initiating the pentose PHOSPHATE shunt, is an important component in generation of NADPH. Although innumerable studies have been performed on human erythrocyte G6PD, however, the effect of trace elements on the enzyme activity requires further investigations. Objective: To study the effect of aluminum on human erythrocyte G6PD. Methods: In this experimental research, following the purification of G6PD using chromatographic methods, the effect of different concentrations of Al3+(up to 100 micro-molar) on G6PD activity was studied. The enzyme activity was measured at different concentrations of GLUCOSE 6-PHOSPHATE and NADP+ to determine the type of inhibitory action. Findings: Aluminum at the concentration of 100 µM showed a considerable inhibitory effect on G6PD activity (60%). The type of inhibitory action, depending on the use of GLUCOSE-6-PHOSPHATE or NADP+, was competitive and noncompetitive, respectively. Conclusion: Aluminum exerts an inhibitory action on human erythrocyte G6PD activity.

Some kinetic properties of NAD+- and NADP+- dependent GLUCOSE 6-PHOSPHATE dehydrogenase (G6PD) purified from streptomyces aureofaciens were studied. Both NADH and NADPH inhibited the enzyme competitively and noncompetitively, with respect to the corresponding coenzymes and GLUCOSE 6-PHOSPHATE, respectively. ATP inhibited the NAD+ - linked reaction but not that of the NADP+- linked activity. The inhibition was competitive with respect to NAD+ and noncompetitive with respect to GLUCOSE 6-PHOSPHATE. Km values were 0.14 mM for NAD+ and 0.075 mM for NADP+. Similar Km values (0.75-0.79 mM) were obtaind for GLUCOSE 6-PHOSPHATE using either NAD+ or NADP+ as a coenzyme. The optimum pH was 6.6 for NAD+- and 7.4 for NADP+- dependent activity. Maximum protein fluorescence was increased by NAD+ (49%) and NADP+ (8%). Among bivalent cations studied, Cu2+ decreased NAD+- linked activity (40%), but increased the NADP+- linked reaction (10%). Ni2+ did not affect NAD+- linked, but stimulated NADP+- linked activity. Other cations such as Zn2+ and Mn2+ also differently affected the two reactions. The data suggested that binding of NAD+ and NADP+ produces a different conformational change in S. aureofaciens G6PD or an isomerisation process regulates coenzyme utilization.

Background: Storage of platelet concentrates (PCs) at room temperature (20-24° C) limits its storage time to 5 Background: GLUCOSE-6-PHOSPHATE dehydrogenase (G6PD) deficiency is the most common inherited enzyme deficiency of the human red blood cells. Most of G6PD deficient individuals are asymptomatic, but acute hemolytic anemia may be presented with nausea, vomiting, abdominal pain, headache, jaundice, pallor, discoloration of the urine, chills, and fever. Seizure is reported as a rare symptom, as well. The present study aimed to investigate seizure following acute hemolysis caused by GLUCOSE-6-PHOSPHATE dehydrogenase deficiency. Material and Methods: This analytic cross-sectional study was conducted on all consecutive patients aged 1-12 years with G6PD deficiency hospitalized for hemolysis in 17 Shahrivar children hospital, Rasht, Iran, in 2016. Demographic characteristics and other variables such as place of inhabitants, type of drinking water, history of seizure in the patients and family, cause of hemolysis, hemoglobin level and hemoglobinuria on admission, and infection history prior to hemolysis were recorded. Data were analyzed by Mann-Whitney U test and Fischer Exact Test. P-value < 0. 05 indicated statistical significance and data were assessed by SPSS (version 20). Results: The youngest patient was one year old and the oldest was 11 years old. Most of them were males (68. 9%). Out of 244 patients, 8 ones (3. 3%) experienced seizure. There was a significant correlation between seizure occurrence and family history of seizure (p=0. 03) as well as fava bean consumption (p=0. 019) as the causes of hemolysis; but not with infection as the cause of hemolysis, hemoglobin or hemoglobinuria level on admission, types of drinking water, place of living, and gender. Methemoglobinemia was considered as the main cause of the seizure. Conclusion: Although the rate of seizure was not so high (3. 3%), it seems that seizure can be a critical and potentially life-threatening complication in these patients. Environmental factors may also play a role in the pathogenesis of the seizure in these patients.

Background: Studies have shown that G6PD deficiency results in indirect hyperbilirubinemia in newborns. Objective: Determining the relationship between G6PD deficiency and neonatal hyperbilirubinemia. Methods: Through a case-control study, 200 neonates with indirect hyperbilirubinemia were equally divided into two case and control groups and examined for G6PD deficiency using a commercial G6PD kit and a fluorometric analysis. The data were further analyzed statistically. Findings: Results showed that out of 200 neonates, 24 had G6PD deficiency (10 in case group and 14 in control group). There was no statistically significant difference between two groups. Conclusion: Since the prevalence of G6PD deficiency among nonicteric group (control group) was higher than the icteric group (case group), it seems that the performance of a screening test to measure the G6PD activity in all neonates to be useful.

Interaction of GLUCOSE 6-PHOSPHATE dehydrogenase from S. aureofaciens with NAD+, NADP+ and GLUCOSE 6-PHOSPHATE were investigated using different fluorescent probes. Binding of NAD+, NADP+ and S-NADPH to the native enzyme quenched intrinsic protein fluorescence by 100%, 10% and 21%, respectively, from which Kd values of NAD+ (6.5 mM), NADP+ (92.0 mM) and S-NADPH (122.0 mM) were calculated. Binding of NAD+, NADP+ and S-NADPH to the pyridoxylated enzyme in which pyridoxal 5`-PHOSPHATE occupied a GLUCOSE 6-PHOSPHATE site, quenched the fluorescence of the pyridoxal group on the enzyme by 20%, 57% and 96%, respectively. Kd values for the pyridoxylated enzyme were also calculated for NAD+ (1.0mM), NADP+ (301.0mM) and S-NADPH (151.0mM). When NAD+ was bound to the native enzyme-S-NADPH complex, to which S-NADPH was bound to only one subunit leaving the other free, the S-NADPH fluorescence was quenched with a 10 nm blue shift in its emission spectrum. NADP+ binding, however, enhanced S-NADPH fluorescence. The fluorescence of S-NADPH bound to the pyridoxylated enzyme was enhanced upon NAD+ binding with a 5 nm blue shift, while NADP+ binding had no effect. A substrate analog, GLUCOSE 1-PHOSPHATE, inhibited the enzyme competitively with respect to GLUCOSE 6-PHOSPHATE and uncompetitively with respect to NAD+. Binding of NAD+ to enzyme-GLUCOSE 1-PHOSPHATE complex quenched protein fluorescence (44%) with decreasing Kd value from 6.5 mM in the absence of GLUCOSE 1-PHOSPHATE to 2.2 mM in its presence. NADP+, however, showed opposite effects. The data demonstrated that S.aureofaciens GLUCOSE 6-PHOSPHATE dehydrogenase undergoes different conformational changes upon NAD+ and NADP+ binding, and modification of GLUCOSE 6-PHOSPHATE binding site by pyridoxal 5`-PHOSPHATE pulls the enzyme in a conformation suitable for NAD+ binding.