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Background Glucose-6-phosphate dehydrogenase (G6PDH or G6PD) functions in supply of NADPH, which is required for plant defense responses to stresses. However, whether G6PD functions in the abscisic acid (ABA) signaling pathway remains to be elucidated. In this study, we investigated the involvement of the cytosolic G6PD5 in the ABA signaling pathway in Arabidopsis . Results We characterized the Arabidopsis single null mutant g6pd5. Phenotypic analysis showed that the mutant is more sensitive to ABA during seed germination and root growth, whereas G6PD5 -overexpressing plants are less sensitive to ABA compared to wild type (WT). Furthermore, ABA induces excessive accumulation of reactive oxygen species (ROS) in mutant seeds and seedlings. G6PD5 participates in the reduction of H 2 O 2 to H 2 O in the ascorbate-glutathione cycle. In addition, we found that G6PD5 suppressed the expression of Abscisic Acid Insensitive 5 ( ABI5 ), the major ABA signaling component in dormancy control. When G6PD5 was overexpressed, the ABA signaling pathway was inactivated. Consistently, G6PD5 negatively modulates ABA-blocked primary root growth in the meristem and elongation zones. Of note, the suppression of root elongation by ABA is triggered by the cell cycle B-type cyclin CYCB1 . Conclusions This study showed that G6PD5 is involved in the ABA-mediated seed germination and root growth by suppressing ABI5 .

Low glucose-6-phosphate dehydrogenase enzyme (G6PD) activity is a key determinant of drug-induced haemolysis. More than 230 clinically relevant genetic variants have been described. We investigated the variation in G6PD activity within and between different genetic variants. In this systematic review, individual patient data from studies reporting G6PD activity measured by spectrophotometry and corresponding the G6PD genotype were pooled (PROSPERO: CRD42020207448). G6PD activity was converted into percent normal activity applying study-specific definitions of 100%. In total, 4320 individuals from 17 studies across 10 countries were included, where 1738 (40.2%) had one of the 24 confirmed G6PD mutations, and 61 observations (3.5%) were identified as outliers. The median activity of the hemi-/homozygotes with A-(c.202G>A/c.376A>G) was 29.0% (range: 1.7% to 76.6%), 10.2% (range: 0.0% to 32.5%) for Mahidol, 16.9% (range 3.3% to 21.3%) for Mediterranean, 9.0% (range: 2.9% to 23.2%) for Vanua Lava, and 7.5% (range: 0.0% to 18.3%) for Viangchan. The median activity in heterozygotes was 72.1% (range: 16.4% to 127.1%) for A-(c.202G>A/c.376A>G), 54.5% (range: 0.0% to 112.8%) for Mahidol, 37.9% (range: 20.7% to 80.5%) for Mediterranean, 53.8% (range: 10.9% to 82.5%) for Vanua Lava, and 52.3% (range: 4.8% to 78.6%) for Viangchan. A total of 99.5% of hemi/homozygotes with the Mahidol mutation and 100% of those with the Mediterranean, Vanua Lava, and Viangchan mutations had <30% activity. For A-(c.202G>A/c.376A>G), 55% of hemi/homozygotes had <30% activity. The G6PD activity for each variant spanned the current classification thresholds used to define clinically relevant categories of enzymatic deficiency.

Docosahexaenoic acid (DHA) is an important omega-3 polyunsaturated fatty acid (PUFA) that plays a critical physiological role in human health. Schizochytrium sp. is considered an excellent strain for DHA production, but the synthesis of DHA is limited by the availability of nicotinamide adenine dinucleotide phosphate (NADPH). In this study, the endogenous glucose-6-phosphate dehydrogenase (G6PD) gene was overexpressed in Schizochytrium sp. H016. Results demonstrated that G6PD overexpression increased the availability of NADPH, which ultimately altered the fatty acid profile, resulting in a 1.91-fold increase in DHA yield (8.81 g/L) and increased carbon flux by shifting it from carbohydrate and protein synthesis to lipid production. Thus, G6PD played a vital role in primary metabolism. In addition, G6PD significantly increased DHA content and lipid accumulation by 31.47% and 40.29%, respectively. The fed-batch fermentation experiment results showed that DHA production reached 17.01 g/L in the overexpressing G6PD strain. These results elucidated the beneficial effects of NADPH on the synthesis of PUFA in Schizochytrium sp. H016, which may be a potential target for metabolic engineering. Furthermore, this study provides a promising regulatory strategy for the large-scale production of DHA in Schizochytrium sp.

Background Glucose-6-Phosphate Dehydrogenase deficiency (G6PDd) is a common genetic enzymopathy that can induce haemolysis triggered by various factors, including some anti-malarial drugs. Although many Point-of-Care (PoC) tests, such as Standard G6PD™ are available to detect G6PDd, its pooled diagnostic test accuracy (DTA) remains unknown. Methods To estimate the DTA of StandG6PD-BS at various thresholds of G6PDd, a systematic review with a DTA meta-analysis were conducted, searching EMBASE, MEDLINE, and SciELO databases up to April 4, 2024.The included studies were those that measured G6PD activity using StandG6PD-BS (reference test) and spectrophotometry (gold standard) in patients suspected of having G6PDd. The risk of bias (RoB) of the studies was assessed using the QUADAS-2 tool and the certainty of evidence (CoE) with the GRADE approach. For the estimation of within-study DTA, a random-effect bivariate meta-analysis was performed to determine the pooled sensitivity and specificity for 30%, 70%, and 80% enzyme levels’ thresholds, and a graphical analysis of the heterogeneity using crosshair and Confidence Regions on receiver operating characteristic (ROC) space plots. Results After screening 2496 reports, four studies were included with 7864 participants covering all thresholds. Two studies had high RoB in QUADAS-2 domains 2 and 3, and the others had low RoB, with low, moderate, and high heterogeneity at the 30%, 70%, and 80% thresholds, respectively. The pooled sensitivity was 99.1%, 95.7%, and 90% for 30%, 70%, and 80% thresholds, respectively. The pooled specificity was 97.4%; 92.9%; and 89.0% for 30%, 70%, and 80% thresholds, respectively. Conclusion StandG6PD-BS is a PoC test with high sensitivity and specificity to detect G6PDd at different thresholds.

Glucose-6-phosphate dehydrogenase (G6PD) insufficiency is a common enzymatic defect worldwide; it affects over 400 million people and is associated with various disorders. Recent research suggests that G6PD-deficient cells are susceptible to infection by human coronaviruses, as the G6PD enzyme is involved in the metabolism of oxidative stress, which may enhance COVID-19 mortality. This retrospective study aimed to examine the effect of COVID-19 on patients with G6PD deficiency by comparing the laboratory parameters of patients with G6PD enzyme deficiency alone, COVID-19 alone, and those with both COVID-19 and G6PD enzyme deficiency treated at a major Saudi tertiary center. The results indicated significant differences in hematological and biochemical parameters between the three patient groups, indicating that COVID-19 may influence these parameters, and that they could be used to measure the severity of COVID-19 disease. Moreover, this study suggests that patients with G6PD enzyme deficiency may be at higher risk for severe COVID-19 outcomes. Although the study is limited by the lack of a random selection method for group membership, the Kruskal–Wallis H-test was used to statistical assess the data. The study’s findings can enhance the understanding of the relation between COVID-19 infected and G6PD-deficiency patients and inform clinical decision making for an improved patient outcome.

Background Current treatment guidelines for radical cure of Plasmodium vivax malaria recommend the use of 8-aminoquinolines, which can result in life-threatening complications in people with glucose-6-phsophate dehydrogenase (G6PD) deficiency. Testing for this condition is recommended prior to administering such drugs. The Wondfo G6PD/Hb Test (Guangzhou Wondfo Biotech Co., Ltd., China) is a novel, quantitative point-of-care (POC) G6PD test that may help decentralize testing, expanding access to safe treatment options. Methods Two studies were conducted: a retrospective diagnostic accuracy study on frozen venous whole blood specimens and a prospective matrix equivalency study. First, 300 frozen specimens from Mae Sot, Thailand were tested from July–August 2022 using the Wondfo test in laboratory and simulated field conditions. Reference testing for G6PD and Hb (spectrophotometer [Pointe Scientific, USA] and HemoCue [HemoCue AB, Sweden], respectively) was completed in the laboratory. Usability was evaluated among 10 intended users. Next, 225 participants were enrolled into a prospective matrix equivalency study from March–May 2023 in Memphis, Tennessee, USA. The Wondfo test was conducted at the POC with fingerstick capillary blood, and Wondfo and HemoCue tests were completed on fresh venous (K 2 EDTA) blood within 12 h. Remaining specimens were shipped to PATH for repeat Wondfo and reference testing. Results The Wondfo G6PD measurement showed strong correlation under both laboratory and field conditions (R 2 >0.9). The area under the curve was 1.00 for deficient (95% CI: 1.00–1.00) and 0.99 for intermediate individuals (95% CI: 0.99–1.00). Sensitivity was high (1.00) across all conditions and groups (lower bound of the 95% CI ≥0.85). Good correlation was observed in both capillary and fresh venous blood against the reference and each other (R 2 >0.75). McNemar’s test showed no significant differences in classification between venous and capillary specimens. The Wondfo test achieved 98.2% (95%CI: 95.5–99.5%) overall agreement. All usability participants successfully completed quality control and test procedures, rating the test system highly for ease of use. Conclusions The Wondfo G6PD/Hb Test demonstrates good diagnostic performance using current manufacturer thresholds across various conditions and both venous and capillary specimens. Comparable performance in both specimen types supports matrix equivalence. Usability is acceptable for end users, though refinements were recommended.

Key message Changes in glucose-6-phosphate dehydrogenase (G6PD) isoforms activities and expression were investigated in soybean roots under drought, suggesting that cytosolic G6PD plays a main role by regulating H 2 O 2 signal and redox homeostasis. G6PD acts a vital role in plant growth, development and stress adaptation. Drought (PEG6000 treatment) could markedly increase the enzymatic activities of cytosolic G6PD ( Cyt-G6PD ) and compartmented G6PD (mainly plastidic P2-G6PD) in soybean roots. Application of G6PD inhibitor upon drought condition dramatically decreased the intracellular NADPH and reduced glutathione levels in soybean roots. Nitric oxide (NO) and hydrogen peroxide (H 2 O 2 ) participated in the regulation of Cyt-G6PD and P2-G6PD enzymatic activities under drought stress. Diphenylene iodonium (DPI), an inhibitor of NADPH oxidase, abolished the drought-induced accumulation of H 2 O 2 . The exogenous application of H 2 O 2 and its production inhibitor (DPI) could stimulate and inhibit the NO accumulation, respectively, but not vice versa. qRT-PCR analysis confirmed that NO, as the downstream signal of H 2 O 2 , positively regulated the transcription of genes encoding Cyt-G6PD ( GPD5 , G6PD6 , G6PD7 ) under drought stress in soybean roots. Comparatively, NO and H 2 O 2 signals negatively regulated the gene expression of compartmented G6PD ( GPD1 , G6PD2 , G6PD4 ), indicating that a post-transcriptional mechanism was involved in compartmented G6PD regulation. Taken together, the high Cyt-G6PD activity is essential for maintaining redox homeostasis upon drought condition in soybean roots, and the H 2 O 2 -dependent NO cascade signal is differently involved in Cyt-G6PD and compartmented G6PD regulation.

Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDd) is an common enzyme deficiency disease, inducing hemolysis, hyperbilirubinemia, and jaundice, as well as liver dysfunction, in approximately 400 million patients. Patients with G6PDd are more susceptible to viruses infection than those without. However, the incidence and severity of hepatitis E virus (HEV) infection in patients with G6PDd are largely unknown. Methods The prevalence of HEV in patients with G6PDd was investigated. Susceptibility to HEV was evaluated in a hepatoma cell line with G6PD knockdown, and the interaction between HEV and G6PD was assessed. Results The prevalence of HEV infection was higher in patients with G6PDd (23.8%, 25/105) than in patients with normal G6PD levels (0.65%, 2/307), indicating that patients with G6PDd are susceptible to HEV infection. Higher rates of hyperbilirubinemia (64% vs. 36.25%) and pneumonia (28% vs. 12.5%) were observed in HEV-infected patients with G6PDd than in patients with normal G6PD values. G6PD knockdown facilitated HEV entry and aggravated oxidative stress with the significant inhibition of glutathione to benefit viral replication but was restricted by NADPH reduction. Co-IP and colocation assays revealed that HEV ORF3 interacted with G6PD. HEV infection stimulated the expression of G6PD in a manner dependent on nuclear factor E2–related factor 2 activation. Consequently, severe apoptosis was observed in HEV-infected cells with G6PD knockdown. Conclusions Patients with G6PDd are susceptible to HEV infection. The facilitation of HEV entry and aggravation of oxidative stress may contribute to HEV susceptibility in patients with G6PDd and severe disease.

Background During early pregnancy, glucose is essential for the uterine epithelium and the developing embryo. In cows, progesterone increases the secretion of glucose into the uterine lumen. The uterine epithelium can convert glucose to fructose, but other fates of glucose in the uterine epithelium have been sparsely investigated. Therefore, our objective was to investigate how progesterone influences glucose metabolism in immortalized bovine uterine epithelial (BUTE) cells. Methods BUTE cells were grown to 80% confluence and treated with vehicle (DMSO) or 10 µM progesterone for 24 h. Cells were collected and analyzed. Immunohistochemistry was performed on endometrial samples collected from the bovine endometrium on days 1 and 11 of the reproductive cycle. Results Progesterone treatment increased glucose consumption of BUTE cells. RNAseq identified 3,072 genes regulated by progesterone. KEGG analysis indicated that progesterone altered genes associated with metabolic pathways and glutathione metabolism. Manually examining genes unique to specific glucose metabolic pathways identified an increase in the rate-limiting enzyme in the pentose phosphate pathway—glucose-6-phosphate dehydrogenase. Functionally, a major product of the pentose phosphate pathway is NADPH, and progesterone treatment increased NADPH levels in BUTE cells. In cows, immunohistochemistry confirmed that glucose-6-phosphate dehydrogenase levels were higher in the uterine epithelium in the luteal phase when progesterone concentrations are high. Conclusions Progesterone increased glucose-6-phosphate dehydrogenase expression and metabolism via the pentose phosphate pathway in the bovine uterine epithelium. This metabolism could provide substrates for cell proliferation, molecules to be secreted into the uterine lumen, or maintain reduction/oxidation balance in the uterine epithelium.

Individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency are at risk of severe haemolysis following the administration of 8-aminoquinoline compounds. Primaquine is the only widely available 8-aminoquinoline for the radical cure of Plasmodium vivax . Tafenoquine is under development with the potential to simplify treatment regimens, but point-of-care (PoC) tests will be needed to provide quantitative measurement of G6PD activity prior to its administration. There is currently a lack of appropriate G6PD PoC tests, but a number of new tests are in development and are likely to enter the market in the coming years. As these are implemented, they will need to be validated in field studies. This article outlines the technical details for the field evaluation of novel quantitative G6PD diagnostics such as sample handling, reference testing and statistical analysis. Field evaluation is based on the comparison of paired samples, including one sample tested by the new assay at point of care and one sample tested by the gold-standard reference method, UV spectrophotometry in an established laboratory. Samples can be collected as capillary or venous blood; the existing literature suggests that potential differences in capillary or venous blood are unlikely to affect results substantially. The collection and storage of samples is critical to ensure preservation of enzyme activity, it is recommended that samples are stored at 4 °C and testing occurs within 4 days of collection. Test results can be visually presented as scatter plot, Bland–Altman plot, and a histogram of the G6PD activity distribution of the study population. Calculating the adjusted male median allows categorizing results according to G6PD activity to calculate standard performance indicators and to perform receiver operating characteristic (ROC) analysis.