An inherent genetic enzyme disorder in humans, known as glucose-6-phosphate dehydrogenase (G6PD) deficiency, arises due to specific mutations. While the prevailing approach for investigating G6PD variants involves biochemical analysis, the intricate structural details remain limited, impeding a comprehensive understanding of how different G6PD variants of varying classes impact their functionality. This study 22 examined the dynamic properties of G6PD wild types and six G6PD variants from 23 different classes using molecular dynamic simulation (MDS). The wild-type and variant 24 G6PD structures unveil high fluctuations within the amino acid range of 274-515, the structural NADP+ binding site, pivotal for enzyme dimerization. Specifically, two variants, G6PDZacatecas (R257L) and G6PDDurham (K238R), demonstrate compromised structural stability at the dimer interface, attributable to the disruption of a salt bridge involving Glu 206 and Lys 407, along with the disturbance of hydrogen bonds formed by Asp 421 at the βN-βN sheets. Consequently, this impairment cascades to affect the binding affinity of crucial interactions, such as Lys 171-Glucose-6-Phosphate (G6P) and Lys 171-catalytic NADP+, leading to diminished enzyme activity. This study underscores the utility of computational in silico techniques in predicting the structural alterations and flexibility of G6PD variants. This insight holds promise for guiding future endeavors in drug development targeted at mitigating the impacts of G6PD deficiency.
The continually expanding global population has necessitated increased food supply production. Thus, agricultural intensification has been required to keep up with food supply demand, resulting in a sharp rise in pesticide use. The pesticide aids in the prevention of potential losses caused by pests, plant pathogens, and weeds, but excessive use over time has accumulated its occurrence in the environment and subsequently rendered it one of the emerging contaminants of concern. This review highlights the sources and classification of herbicides and their fate in the environment, with a special focus on the effects on human health and methods to remove herbicides. The human health impacts discussion was in relation to toxic effects, cell disruption, carcinogenic impacts, negative fertility effects, and neurological impacts. The removal treatments described herein include physicochemical, biological, and chemical treatment approaches, and advanced oxidation processes (AOPs). Also, alternative, green, and sustainable treatment options were discussed to shed insight into effective treatment technologies for herbicides. To conclude, this review serves as a stepping stone to a better environment with herbicides.
Accurate diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency is crucial for relapse malaria treatment using 8-aminoquinolines (primaquine and tafenoquine), which can trigger haemolytic anaemia in G6PD-deficient individuals. This is particularly important in regions where the prevalence of G6PD deficiency exceeds 3%-5%, including Southeast Asia and Thailand. While quantitative phenotypic tests can identify women with intermediate activity who may be at risk, they cannot unambiguously identify heterozygous females who require appropriate counselling. This study aimed to develop a genetic test for G6PD deficiency using high-resolution melting curve analysis, which enables zygosity identification of 15 G6PD alleles. In 557 samples collected from four locations in Thailand, the prevalence of G6PD deficiency based on indirect enzyme assay was 6.10%, with 8.08% exhibiting intermediate deficiency. The developed high-resolution melting assays demonstrated excellent performance, achieving 100% sensitivity and specificity in detecting G6PD alleles compared with Sanger sequencing. Genotypic variations were observed across four geographic locations, with the combination of c.1311C>T and c.1365-13T>C being the most common genotype. Compound mutations, notably G6PD Viangchan (c.871G>A, c.1311C>T and c.1365-13T>C), accounted for 15.26% of detected mutations. The high-resolution melting assays also identified the double mutation G6PD Chinese-4 + Canton and G6PD Radlowo, a variant found for the first time in Thailand. Biochemical and structural characterisation revealed that these variants significantly reduced catalytic activity by destabilising protein structure, particularly in the case of the Radlowo mutation. The refinement of these high-resolution melting assays presents a highly accurate and high-throughput platform that can improve patient care by enabling precise diagnosis, supporting genetic counselling and guiding public health efforts to manage G6PD deficiency-especially crucial in malaria-endemic regions where 8-aminoquinoline therapies pose a risk to deficient individuals.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy in humans that may exacerbate clinical outcomes during viral infections such as dengue, particularly in regions where both conditions are endemic. This study aimed to characterize the spectrum of G6PD mutations and explore trends in hemoglobin levels among adult dengue patients in Thailand. Samples from 231 adult patients diagnosed with dengue were analyzed. G6PD deficiency was identified in 24 individuals (10.4%), while G6PD mutations were detected in 111 patients (48.1%). The most frequently observed mutations include a combination of synonymous and intronic mutations (c.1311C > T and c.1365-13T > C), compound mutation of G6PD Viangchan (c. 871G > A, c.1311C > T and c.1365-13T > C), and a deletion variant (c.486-34delT). Additionally, a novel variant, c.1439T > C, was identified and named "G6PD Phaya Thai". Patients carrying G6PD mutations exhibited different hemoglobin level trends compared to those without mutations. Specifically, while hemoglobin levels increased from the febrile to critical phase in patients without mutations, a significant decline was observed in mutation carriers. Median hemoglobin levels differed significantly between the two groups during both the febrile and critical phases (p = 0.02 and p