Glucose-6-phosphate Dehydrogenase Enzyme Research Articles

Glucose-6-Phosphate Dehydrogenase Status in the Term Newborns and Their Clinical and Other Laboratory Correlates

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme defect in man. Though G6PD deficiency affects every cell in the body, its primary effects are hematological.
 Objectives: The objectives of the study were to determine the G6PD enzyme concentration and deficiency states among the term newborns, to see the impact of the enzyme status with development of neonatal jaundice and to delineate any correlation of the G6PD with other hematological values.
 Materials and Method: Total 100 term newborns were enrolled in the study. Umbilical cord blood sample from the placental end were collected for G6PD enzyme assay, blood counts including reticulocyte count, blood indices and bilirubin estimation. Clinical and other relevant data were collected. Statistical analysis was done by using SPSS 19.0 version.
 Results: Overall G6PD activity was detected 9.86 ± 1.68 U/g Hb and no G6PD enzyme deficiency state was identified. There were no statistically significant differences in the hematological parameters and cord blood bilirubin concentration between male and females. But females have significantly higher G6PD enzyme concentration than males (p=0.002). There were no significant differences in the enzyme concentration in different gestational age groups. There was significant negative correlation between G6PD enzyme and hemoglobin levels, G6PD enzyme concentration with HCT and MCV values.
 Conclusion: This study could not identify any G6PD deficiency state. So further large scale community-based study is needed to validate this finding and also establish the normal G6PD enzyme concentration in the population of Bangladesh.
 Bangladesh J Child Health 2020; VOL 44 (1) :18-23

Identification of the Cytosolic Glucose-6-Phosphate Dehydrogenase Gene from Strawberry Involved in Cold Stress Response.

Glucose-6-phosphate dehydrogenase (G6PDH) plays an important role in plant stress responses. Here, five FaG6PDH sequences were obtained in strawberry, designated as FaG6PDH-CY, FaG6PDH-P1, FaG6PDH-P1.1, FaG6PDH-P2 and FaG6PDH-P0, which were divided into cytosolic (CY) and plastidic (P) isoforms based on the bioinformatic analysis. The respective FaG6PDH genes had distinct expression patterns in all tissues and at different stages of fruit development. Notably, FaG6PDH-CY was the most highly expressed gene among five FaG6PDH members, indicating it encoded the major G6PDH isoform throughout the plant. FaG6PDH positively regulated cold tolerance in strawberry. Inhibition of its activity gave rise to greater cold-induced injury in plant. The FaG6PDH-CY transcript had a significant increase under cold stress, similar to the G6PDH enzyme activity, suggesting a principal participant in response to cold stress. Further study showed that the low-temperature responsiveness (LTR) element in FaG6PDH-CY promoter can promote the gene expression when plant encountered cold stimuli. Besides, FaG6PDH-CY was involved in regulating cold-induced activation of antioxidant enzyme genes (FaSOD, FaCAT, FaAPX and FaGR) and RBOH-dependent ROS generation. The elevated FaG6PDH-CY enhanced ROS-scavenging capability of antioxidant enzymes to suppress ROS excessive accumulation and relieved the oxidative damage, eventually improving the strawberry resistance to cold stress.

The effects on antioxidant enzymes of PMMA/hydroxyapatite nanocomposites/composites

In this study, polymer-ceramic nanocomposites and/or composites were prepared by solution removal method using poly(methylmethacrylat) (PMMA) and nano-hydroxyapatite (nHA). They were characterized using X-ray diffraction (XRD), Fourier transform infrared-attenuated total reflection spectroscopy (FTIR-ATR), and differential thermal analysis/thermogravimetry (DTA/TG). Their effects and biocompatibilities on antioxidant enzymes were also investigated in detail. It has been shown that nHA was dramatically dispersed at nanoscale in the polymer matrix. The interaction occurred between OH groups of nHA and carbonyl groups of polymer and introduction of ceramic into the polymer matrix generally resulted in an increase in thermal stability. Nanocomposites and composites had different effects on enzyme activities. Samples synthesized in acetone increased enzyme activities for glutathione reductase (GR) and glucose-6 phosphate dehydrogenase (G6PD) enzymes, while inhibiting glutathione peroxidase (GPx) and catalase (CAT) enzyme activities. On the other hand, samples synthesized in tetrahydrofuran (THF) exhibited inhibitory behavior for G6PD and CAT enzymes. The samples synthesized in different media did not show any regularity on enzyme activities. The nanocomposites and/or composites prepared in acetone media were better hemocompatible than those in THF.

Tafenoquine for preventing relapse in people with Plasmodium vivax malaria.

Plasmodium vivax malaria has a persistent liver stage that causes relapse of the disease and continued P vivax transmission. Primaquine (PQ) is used to clear the liver stage of the parasite, but treatment is required for 14 days. Primaquine also causes haemolysis in people with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Tafenoquine (TQ) is a new alternative to PQ with a longer half-life and can be used as a single-dose treatment. To assess the effects of tafenoquine 300 mg (single dose) on preventing P vivax relapse. We searched the following up to 3 June 2020: the Cochrane Infectious Diseases Group Specialized Register; CENTRAL; MEDLINE; Embase; and three other databases. We also searched the WHO International Clinical Trial Registry Platform and the metaRegister of Controlled Trials for ongoing trials using "tafenoquine" and "malaria" as search terms up to 3 June 2020. Randomized controlled trials (RCTs) that gave TQ to prevent relapse in people with P vivax malaria. We planned to include trials irrespective of whether participants had been screened for G6PD enzyme deficiency. All review authors independently extracted data and assessed risk of bias. As true relapse and reinfection are difficult to differentiate in people living in endemic areas, studies report "recurrences" of infection as a proxy for relapse. We carried out meta-analysis where appropriate, and gave estimates as risk ratios (RR) with 95% confidence intervals (CI). We assessed the certainty of the evidence using the GRADE approach. Three individually randomized RCTs met our inclusion criteria, all in endemic areas, and thus reporting recurrence. Trials compared TQ with PQ or placebo, and all participants received chloroquine (CQ) to treat the asexual infection). In all trials, pregnant and G6PD-deficient people were excluded. Tafenoquine 300 mg single dose versus no treatment for relapse prevention Two trials assessed this comparison. TQ 300 mg single dose reduces P vivax recurrences compared to no antihypnozoite treatment during a six-month follow-up, but there is moderate uncertainty around effect size (RR 0.32, 95% CI 0.12 to 0.88; 2 trials, 504 participants; moderate-certainty evidence). In people with normal G6PD status, there is probably little or no difference in any type of adverse events (2 trials, 504 participants; moderate-certainty evidence). However, we are uncertain if TQ causes more serious adverse events (2 trials, 504 participants; very low-certainty evidence). Both RCTs reported a total of 23 serious adverse events in TQ groups (One RCT reported 21 events) and a majority (15 events) were a drop in haemoglobin level by > 3g/dl (or >30% reduction from baseline). Tafenoquine 300 mg single dose versus primaquine 15 mg/day for 14 days for relapse prevention Three trials assessed this comparison. There is probably little or no difference between TQ and PQ in preventing recurrences (proxy measure for relapse) up to six months of follow-up (RR 1.04, 95% CI 0.8 to 1.34; 3 trials, 747 participants; moderate-certainty evidence). In people with normal G6PD status, there is probably little or no difference in any type of adverse events (3 trials, 747 participants; moderate-certainty evidence). We are uncertain if TQ can cause more serious adverse events compared to PQ (3 trials, 747 participants; very low-certainty evidence). Two trials had higher point estimates against TQ while the other showed the reverse. Most commonly reported serious adverse event in TQ group was a decline in haemoglobin level (19 out of 29 events). Some other serious adverse events, though observed in the TQ group, are unlikely to be caused by it (Hepatitis E infection, limb abscess, pneumonia, menorrhagia). TQ 300 mg single dose prevents relapses after clinically parasitologically confirmed P vivax malaria compared to no antihypnozoite treatment, and with no difference detected in studies comparing it to PQ to date. However, the inability to differentiate a true relapse from a recurrence in the available studies may affect these estimates. The drug is untested in children and in people with G6PD deficiency. Single-dose treatment is an important practical advantage compared to using PQ for the same purpose without an overall increase in adverse events in non-pregnant, non-G6PD-deficient adults.

Possible inhibition mechanism of dobutamine hydrochloride as potent inhibitor for human glucose-6-phosphate dehydrogenase enzyme

Glucose-6-phosphate dehydrogenase (G6PD) is the first rate-limiting enzyme in the pentose phosphate pathway. One of the enzyme’s most important functions is the production of a reducing agent that is essential for preserving the level of reduced glutathione (GSH). However, some chemicals, such as industrial waste and the active ingredients of several drugs, can cause reduction or blockage in this enzyme’s activity. This case causes the occurrence of anemia by damaging erythrocytes. In this study, the G6PD enzyme was purified 21,981 fold with affinity chromatography and the effects of the active ingredients of some antiarrhythmic drugs on enzyme activity were investigated with in vitro and in silico methods. We found that dobutamine hydrochloride significantly decreased enzyme activity and its inhibitory constant (Ki ) value was calculated as 19.02 ± 4.83 mM. The in vitro study results also show that dobutamine hydrochloride is a potent inhibitor of enzyme activity. We also found that dobutamine hydrochloride inhibits the hG6PD enzyme’s activity by causing structural alterations in substrate and coenzyme binding sites. Communicated by Ramaswamy H. Sarma

Glucose-6-Phosphate Dehydrogenase Deficiency and the Benefits of Early Screening.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common enzymopathy worldwide, is an insufficient amount of the G6PD enzyme, which is vital to the protection of the erythrocyte. Deficient enzyme levels lead to oxidative damage, hemolysis, and resultant severe hyperbilirubinemia. If not promptly recognized and treated, G6PD deficiency can potentially lead to bilirubin-induced neurologic dysfunction, acute bilirubin encephalopathy, and kernicterus. Glucose-6-phosphate dehydrogenase deficiency is one of the three most common causes for pathologic hyperbilirubinemia. A change in migration patterns and intercultural marriages have created an increased incidence of G6PD deficiency in the United States. Currently, there is no universally mandated metabolic screening or clinical risk assessment tool for G6PD deficiency in the United States. Mandatory universal screening for G6PD deficiency, which includes surveillance and hospital-based risk assessment tools, can identify the at-risk infant and foster early identification, diagnosis, and treatment to eliminate neurotoxicity.

Frequency of Human Paraoxonase-1 Q192R Polymorphism and Measurement of Oxidative Stress Parameters in Infants with G6PD Deficiency

Background and Aims: This study aimed to investigate the frequency of Q192R polymorphism and oxidative stress markers in infants with glucose-6phosphate dehydrogenase (G6PD) deficiency.
 Materials and Methods: This is a case-control study in which 60 male infants (2-4 months old) with G6PD deficiency along with 60 age- and sexmatched healthy neonates were included. The diagnosis of G6PD deficiency was made by Beutler test by which the G6PD enzyme activity is measured by the fluorescent spot test. The blood samples were taken from all infants, and the sera were isolated for the evaluation of Paraoxonase-1 (PON1) and malondialdehyde (MDA) using the spectrophotometric method. Restriction fragment length polymorphism was applied for determination of Q192R polymorphism (rs 662).
 Results: The frequencies of QQ, QR, and RR genotypes were 55%, 39%, and 6%, respectively in infants with G6PD deficiency while the above genotype frequencies were 45%, 49%, and 6%, respectively in healthy neonates. The frequency of R and T alleles failed to show any significant difference when G6PD deficient infants and healthy neonates were compared. The results indicated PON1 activity and MDA levels being significantly (p<0.05) higher in neonates with G6PD deficiency compared with their healthy counterparts.
 Conclusion: Contrary to previous studies, it was indicated that the presence of RQ and RR genotypes at Q192R position is associated with decreased activity of PON1 and increased oxidative stress. In this study, no significant differences were found in the genotype and allele frequency of PON1 Q192R polymorphism between the case and control groups. Also, this frequency was not consistent with the results obtained from oxidative stress conditions.

Genome-Wide Analysis of the Glucose-6-Phosphate Dehydrogenase Family in Soybean and Functional Identification of GmG6PDH2 Involvement in Salt Stress.

Glucose-6-phosphate dehydrogenase (G6PDH) is known as a critical enzyme responsible for nicotinamide adenine dinucleotide phosphate (NADPH) generation in the pentose phosphate pathway (PPP), and has an essential function in modulating redox homeostasis and stress responsiveness. In the present work, we characterized the nine members of the G6PDH gene family in soybean. Phylogenic analysis and transit peptide prediction showed that these soybean G6PDHs are divided into plastidic (P) and cytosolic (Cy) isoforms. The subcellular locations of five GmG6PDHs were further verified by confocal microscopy in Arabidopsis mesophyll protoplasts. The respective GmG6PDH genes had distinct expression patterns in various soybean tissues and at different times during seed development. Among them, the Cy-G6PDHs were strongly expressed in roots, developing seeds and nodules, while the transcripts of P-G6PDHs were mainly detected in green tissues. In addition, the activities and transcripts of GmG6PDHs were dramatically stimulated by different stress treatments, including salt, osmotic and alkali. Notably, the expression levels of a cytosolic isoform (GmG6PDH2) were extraordinarily high under salt stress and correlated well with the G6PDH enzyme activities, possibly implying a crucial factor for soybean responses to salinity. Enzymatic assay of recombinant GmG6PDH2 proteins expressed in Escherichia coli showed that the enzyme encoded by GmG6PDH2 had functional NADP+-dependent G6PDH activity. Further analysis indicated overexpression of GmG6PDH2 gene could significantly enhance the resistance of transgenic soybean to salt stress by coordinating with the redox states of ascorbic acid and glutathione pool to suppress reactive oxygen species generation. Together, these results indicate that GmG6PDH2 might be the major isoform for NADPH production in PPP, which is involved in the modulation of cellular AsA-GSH cycle to prevent the oxidative damage induced by high salinity.

A cross-sectional study on parental awareness for newborn screening and assessment of the burden of congenital hypothyroidism and glucose 6-phosphate dehydrogenase deficiency

Introduction: Newborn Screening (NBS) has been one of the most successful health programs and of most paramount importance worldwide but not so in India. Due to the lack of awareness and paucity of laboratory facilities, the disease burden in our population has not yet been established. Aim and Objective: The aim and objective of the study was to assess the burden of Congenital Hypothyroidism (CH) and Glucose 6-Phosphate Dehydrogenase (G6PD) deficiency in this area by NBS tests and to assess the impact of awareness sessions on the response rate of parents for NBS. Material and Methods: The screening was conducted in 474 babies of age 48 h up to 8 weeks. The dried blood spots collected were subjected to the following analytical protocol. Thyroid-stimulating hormone (TSH) level and G6PD enzyme activity were analyzed by immunofluorescence method-based neonatal kits. All babies with a positive screening test for G6PD deficiency and CH were asked for venous confirmatory testing after 7 days. Results: The efficiency of the program for all live birth babies delivered in the institute was 92% (n = 410/445). It was 82% in the first phase of the study period and 98.5% in the second phase. Repeated training of nursing professional reduced the sampling errors from 14.7% in the first phase to 6.1% in the second phase. A total of 11 samples reflected high TSH values, of which one baby confirmed for CH. Of the 24 babies who screened positive for G6PD, four were confirmed for the same. The prevalence for CH and G6PD deficiency was, respectively, 1 in 462 (2/1000) and 4 in 462 (8.7/1000). Conclusion: Development of expansion of NBS program in the state should be made mandatory for all newborns. The recommendations include awareness among parents, during antenatal and postnatal period and also to health professionals and provision for laboratory facilities for NBS testing at low cost.

Study of G6pd Deficit (Glucose-6-phosphate Deshydrogenase) in Blood Donors in Brazzaville

Glucose-6-Phosphate dehydrogenase (G6PD) is an enzyme present in the cytoplasm of all cells in the body and protects red blood cells from certain attacks. The anomaly is genetically inherited in a recessive manner, linked to the X chromosome. Currently, an estimated 420 million individuals lack G6PD worldwide and its incidence varies between 1-25% in some African populations. This was an analytical cross-sectional study with prospective data collection that took place from May to November 2018, i.e. six (6) months. Our study included 108 blood donors, 88 men and 20 women. The samples were stored at 2-8 ° C for 24 hours while awaiting handling. The determination of the enzymatic activity of G6PD was carried out by the spectrophotometric method using a commercially available kit. 02/108 subjects studied (ie a prevalence of 1.85%) were deficient in our study. These two deficit were mostly young and between 18-25 years old only male. They were originally from the plateau and observed in the blood transfusion station (PTS) of the Talangai referral hospital. The mean hemoglobin value in normal subjects was 12.53 g / dl in men and 11.3 g / dl in women. In contrast, the average hemoglobin value was 10.45 g / dl in the deficient patients. The mean value of G6PD enzyme activity in normal subjects was 11.7 IU / g hemoglobin in men, 11.54 IU / g hemoglobin in women and in deficient subjects was 2.83 IU / g hemoglobin. As the results of our study show, G6PD deficiency affects hemoglobin levels.

Evidence of positively selected G6PD A- allele reduces risk of Plasmodium falciparum infection in African population on Bioko Island.

BackgroundGlucose‐6‐phosphate dehydrogenase (G6PD) is an essential enzyme that protects red blood cells from oxidative damage. Although G6PD‐deficient alleles appear to confer a protective effect of malaria, the link with clinical protection against Plasmodium infection is conflicting.MethodsA case–control study was conducted on Bioko Island, Equatorial Guinea and further genotyping analysis used to detect natural selection of the G6PD A‐ allele.ResultsOur results showed G6PD A‐ allele could significantly reduce the risk of Plasmodium falciparum infection in male individuals (adjusted odds ratio [AOR], 0.43; 95% confidence interval [CI], 0.20–0.93; p < .05) and homozygous female individuals (AOR, 0.11; 95% CI, 0.01–0.84; p < .05). Additionally, the parasite densities were significantly different in the individuals with different G6PD A‐ alleles and individual levels of G6PD enzyme activity. The pattern of linkage disequilibrium and results of the long‐range haplotype test revealed a strong selective signature in the region encompassing the G6PD A‐ allele over the past 6,250 years. The network of inferred haplotypes suggested a single origin of the G6PD A‐ allele in Africans.ConclusionOur findings demonstrate that glucose‐6‐phosphate dehydrogenase (G6PD) A‐ allele could reduce the risk of P. falciparum infection in the African population and indicate that malaria has a recent positive selection on G6PD A‐ allele.

Effects of butylparaben on antioxidant enzyme activities and histopathological changes in rat tissues.

Butyl p-hydroxybenzoic acid, also known as butylparaben (BP), is one of the most common parabens absorbed by the skin and gastrointestinal tract and metabolised in the liver and kidney. Recent in vivo and in vitro studies have raised concern that BP causes reproductive, development, and teratogenic toxicity. However, BP-induced oxidative stress and its relation to tissue damage has not been widely investigated before. Therefore, we aimed to investigate the effects of butyl 4-hydroxybenzoate on enzyme activities related to the pentose phosphate pathway and on glutathione-dependent enzymes such as glucose 6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6-PGD), glutathione reductase (GR), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) in kidney, liver, brain, and testis tissues. Male rats were randomly divided into four groups to orally receive corn oil (control) or 200, 400, or 800 mg/kg/day of BP for 14 days. Then we measured G6PD, GR, GST, 6-PGD, and GPx enzyme activities in these tissues and studied histopathological changes. BP treatment caused imbalance in antioxidant enzyme activities and tissue damage in the liver, kidney, brain, and testis. These findings are the first to show the degenerative role of BP on the cellular level. The observed impairment of equivalent homeostasis and antioxidant defence points to oxidative stress as a mechanism behind tissue damage caused by BP.

The pentose phosphate pathway regulates chronic neuroinflammation and dopaminergic neurodegeneration

BackgroundMetabolic dysfunction and neuroinflammation are increasingly implicated in Parkinson’s disease (PD). The pentose phosphate pathway (PPP, a metabolic pathway parallel to glycolysis) converts glucose-6-phosphate into pentoses and generates ribose-5-phosphate and NADPH thereby governing anabolic biosynthesis and redox homeostasis. Brains and immune cells display high activity of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP. A postmortem study reveals dysregulation of G6PD enzyme in brains of PD patients. However, spatial and temporal changes in activity/expression of G6PD in PD remain undetermined. More importantly, it is unclear how dysfunction of G6PD and the PPP affects neuroinflammation and neurodegeneration in PD.MethodsWe examined expression/activity of G6PD and its association with microglial activation and dopaminergic neurodegeneration in multiple chronic PD models generated by an intranigral/intraperitoneal injection of LPS, daily subcutaneous injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 6 days, or transgenic expression of A53T α-synuclein. Primary microglia were transfected with G6PD siRNAs and treated with lipopolysaccharide (LPS) to examine effects of G6PD knockdown on microglial activation and death of co-cultured neurons. LPS alone or with G6PD inhibitor(s) was administrated to mouse substantia nigra or midbrain neuron-glia cultures. While histological and biochemical analyses were conducted to examine microglial activation and dopaminergic neurodegeneration in vitro and in vivo, rotarod behavior test was performed to evaluate locomotor impairment in mice.ResultsExpression and activity of G6PD were elevated in LPS-treated midbrain neuron-glia cultures (an in vitro PD model) and the substantia nigra of four in vivo PD models. Such elevation was positively associated with microglial activation and dopaminergic neurodegeneration. Furthermore, inhibition of G6PD by 6-aminonicotinamide and dehydroepiandrosterone and knockdown of microglial G6PD attenuated LPS-elicited chronic dopaminergic neurodegeneration. Mechanistically, microglia with elevated G6PD activity/expression produced excessive NADPH and provided abundant substrate to over-activated NADPH oxidase (NOX2) leading to production of excessive reactive oxygen species (ROS). Knockdown and inhibition of G6PD ameliorated LPS-triggered production of ROS and activation of NF-кB thereby dampening microglial activation.ConclusionsOur findings indicated that G6PD-mediated PPP dysfunction and neuroinflammation exacerbated each other mediating chronic dopaminergic neurodegeneration and locomotor impairment. Insight into metabolic-inflammatory interface suggests that G6PD and NOX2 are potential therapeutic targets for PD.

G6PD Deficiency Prevalence as a Cause of Neonatal Jaundice in a Neonatal Ward in Dohuk, Iraq.

The current study initiated to address the effect of glucose-6-phosphate dehydrogenase (G6PD) deficiency on the pathogenesis and the severity of neonatal hyperbilirubinemia (NHB). A total of 100 newborns with moderate to severe indirect hyperbilirubinemia and 50 normal neonates without hyperbilirubinemia had been enrolled in the current case-control study. All enrolled neonates had been tested for ABO and Rh(D) blood grouping, Total serum bilirubin measurement, complete blood count, morphology, reticulocyte counts, direct Coombs' test, and G6PD enzyme assay. From all enrolled hyperbilirubinemic neonates, 16% were G6PD deficient and this displays a statistically significant difference in comparison to controls (only 6% were G6PD deficient). Also, significant difference was found in the level of serum indirect bilirubin among G6PD-deficient neonate in comparison to G6PD nondeficient neonates which had contributed significantly to the difference in the duration of phototherapy and hospitalization among deficient neonate. Despite this, no significant difference found in the onset of presentation, reticulocytes count, and age of neonates between the two groups (G6PD-deficient and G6PD nondeficient neonates). The current study augments the etiological role of G6PD in the causation and severity of NHB in the region; however, in the absence of significant difference in the reticulocytes and the hemoglobin level, the underlying mechanism cannot be backed to the excess hemolysis alone.

G6PD deficiency: An update.

Although glucose-6-phosphate dehydrogenase (G6PD) deficiency is less known in Western countries than in the Middle East and Africa, global migration and immigration are bringing ethnic groups with the highest incidence of this inherited genetic disorder into the US healthcare system. The G6PD enzyme is critical to protecting erythrocytes against oxidative stress, and deficiency may lead to hemolysis in the presence of certain environmental factors such as infection and some medications and foods. Neonatal jaundice, favism, and hemolysis are associated with exposure to increased oxidative stressors in patients with G6PD deficiency. By recognizing the potential for G6PD deficiency, clinicians can screen for the disorder and teach affected patients how to avoid triggers that result in harmful clinical manifestations.

STUDY OF GLUCOSE-6-PHOSPHATE DEHYDROGENASE ENZYME AND ISOPROSTANE ON PREECLAMPSIA WITH NIFEDIPINE, METHYLDOPA, AND MAGNESIUM SULFATE THERAPY

Objective: The objective of this research is to measure erythrocyte glucose-6-phosphate dehydrogenase (G6PD) enzyme activity and isoprostane andto correlate enzyme activity of G6PD with proteinuria and isoprostane in pregnant with proteinuria after the administration of nifedipine, methyldopa,and magnesium sulfate.Methods: This cross-sectional study was held in Soewandi Hospital, Surabaya, East Java, Indonesia. This study used total sampling as much as 30pregnant women with proteinuria who got nifedipine, methyldopa, and magnesium sulfate administration, age ranged from 17 to 48 years during theirthird trimester (&gt;20 weeks). G6PD enzyme activity was measured from plasma by spectrophotometric method; plasma isoprostane was measuredby competitive-ELISA method; and proteinuria urine spot was analyzed by urine dipstick from standardized laboratory of the hospital. Statisticalanalysis used in this study was Spearman’s correlation coefficient.Results: In this research, the effect of proteinuria +1 (OR=0.056) is lower than proteinuria +3 level on the presence of high G6PD enzyme activity,and proteinuria +2 (OR=0.933) is lower than proteinuria +3 level on the presence of high G6PD enzyme activity in pregnant women with proteinuria.G6PD enzyme was positively correlated (p=0.08) with proteinuria, and the connection was statistically significant. There was no significant statisticcorrelation between G6PD enzyme activity and isoprostane concentration (p=0.797).Conclusion: This study found correlations between the enzyme activity of G6PD and proteinuria as the marker of renal damage in pre-eclampsia (PE)with the administration of nifedipine, methyldopa, and magnesium sulfate. However, it had no correlation with isoprostane as the marker of oxidativestress. This study suggests that there should be a concern about understanding the pathophysiology of proteinuria for possibility of drug target forindividuals with PE.

The Synthesis of Thiosemicarbazone-Based Aza-Ylides as Inhibitors of Rat Erythrocyte Glucose 6-Phosphate Dehydrogenase Enzyme

Glucose 6-phosphate dehydrogenase (G6PD) enzyme plays an important role in various biochemical processes such as synthesis of cholesterol, fatty acids, sphingosine, steroid hormones, NADPH, some amino acids and ribose 5-phosphate. In this study, thiosemicarbazone-based aza-ylide (TSCAs) derivatives 3a-3e, which form the main framework of many drugs such as thioacetazone, ambazone, and perchlozone, were synthesized with a green approach and in vitro inhibitor or activator effects on G6PD enzyme activity was investigated. As a result of studies, TSCAs derivatives 3a-3d inhibited the G6PD enzyme activity with IC50 in the range of 40.77 μM to 58.0 μM for G6PD.

Inhibition effects of some antidepressant drugs on pentose phosphate pathway enzymes

The glucose metabolism in the pentose cycle is essential to the source of NADPH. Deficiency of these enzymes have been linked to depression and psychotic disorders. Depression is an increasingly prevalent mental disorder which may cause loss of labor. Antidepressant drugs are commonly employed in treatments of mood disorders and anxiety treatment. The purpose of this study is to investigate the effects of aripiprazole, mirtazapine, risperidone, escitalopram and haloperidol on the activity of 6-phosphogluconate dehydrogenase (6PGD) and glucose-6-phosphate dehydrogenase (G6PD) enzymes purified from human erythrocytes. It was found that aripiprazole, mirtazapine, risperidone, escitalopram and haloperidol show effective inhibitor properties on purified G6PD and 6PGD enzymes. The IC50 values of these drugs were found in the range of 26.34 μM-5.78 mM for 6PGD and 16.26 μM-3.85 mM for G6PD. The Ki values of the drugs were found in the range of 30.21 ± 4.31 μM-4.51 ± 1.83 mM for 6PGD and 14.12 ± 3.48 μM-4.98 ± 1.14 mM for G6PD. Usage of drugs with significant biological effects may be a hazard in some conditions.

Surfaces based on amino acid functionalized polyelectrolyte films towards active surfaces for enzyme immobilization.

Surface based on polyelectrolytes functionalized with amino acids onto amino-terminated solid surfaces of silicon wafers was prepared, with the purpose of evaluate the chemical functionality of the polyelectrolyte films in adsorption and catalytic activity of an enzyme. In this work, the adsorption of the enzyme glucose 6-phosphate dehydrogenase from Leuconostoc mesenteroides (LmG6PD) was studied as model. The polyelectrolytes were obtained from poly (maleic anhydride-alt-vinylpyrrolidone) [poly(MA-alt-VP)] and functionalized with amino acids of different hydropathy index: glutamine (Gln), tyrosine (Tyr) and methionine (Met). The polyelectrolytes were adsorbed onto the amino-terminated silicon wafer at pH 3.5 and 4.5 and at low and high ionic strength. At low ionic strength and pH 3.5, the largest quantity of adsorbed polyelectrolyte was on the films containing glutamine moiety as the most hydrophilic amino acid in the side chain of polymer chain (5.88 mg/m2), whereas at high ionic strength and pH 4.5, the lowest quantity was in films containing tyrosine moiety in the side chain (1.88 mg/m2). The films were characterized by ellipsometry, contact angle measurements and atomic force microscopy (AFM). The polyelectrolyte films showed a moderate degree of hydrophobicity, the methionine derivative being the most hydrophobic film. With the aim of evaluate the effect of the amino acid moieties on the ability of the surface to adsorb enzymes, we study the activity of the enzyme on these surfaces. We observed that the polarity of the side chain of the amino acid in the polyelectrolyte affected the quantity of LmG6PD adsorbed, as well as its specific activity, showing that films prepared from poly(MA-alt-VP) functionalized with Met provide the best enzymatic performance. The results obtained demonstrated that the surfaces prepared from polyelectrolytes functionalized with amino acids could be an attractive and simple platform for the immobilization of enzymes, which could be of interest for biocatalysis applications.

Transient liver injury and severe neonatal cholestasis in infant with glucose-6-phosphate dehydrogenase deficiency due to a new mutation

We report the case of a neonate with a new, previously undescribed, glucose-6-phosphate dehydrogenase (G6PD) gene mutation, which was revealed by severe cholestasis, hyperbilirubinemia, and transient liver dysfunction. The severity of the clinical phenotype with ongoing chronic hemolytic anemia suggests that this mutation belongs to class 1 G6PD deficiency. The hemizygous mutation «c.675G>c; p.Trp225Cys» was detected by genomic sequencing. Since severe G6PD deficiency can be revealed by cholestasis, it is important to check G6PD enzyme activity when faced with a case of liver dysfunction in the neonatal period.