Fused Enzyme Glucose-6-Phosphate Dehydrogenase::6-Phosphogluconolactonase (G6PD::6PGL) as a Potential Drug Target in Giardia lamblia, Trichomonas vaginalis, and Plasmodium falciparum.

Several microaerophilic parasites such as Giardia lamblia, Trichomonas vaginalis, and Plasmodium falciparum are major disease-causing organisms and are responsible for spreading infections worldwide. Despite significant progress made in understanding the metabolism and molecular biology of microaerophilic parasites, chemotherapeutic treatment to control it has seen limited progress. A current proposed strategy for drug discovery against parasitic diseases is the identification of essential key enzymes of metabolic pathways associated with the parasite's survival. In these organisms, glucose-6-phosphate dehydrogenase::6-phosphogluconolactonase (G6PD:: 6PGL), the first enzyme of the pentose phosphate pathway (PPP), is essential for its metabolism. Since G6PD:: 6PGL provides substrates for nucleotides synthesis and NADPH as a source of reducing equivalents, it could be considered an anti-parasite drug target. This review analyzes the anaerobic energy metabolism of G. lamblia, T. vaginalis, and P. falciparum, with a focus on glucose metabolism through the pentose phosphate pathway and the significance of the fused G6PD:: 6PGL enzyme as a therapeutic target in the search for new drugs.

An Overall View of the Functional and Structural Characterization of Glucose-6-Phosphate Dehydrogenase Variants in the Mexican Population.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, affecting an estimated 500 million people worldwide, is a genetic disorder that causes human enzymopathies. Biochemical and genetic studies have identified several variants that produce different ranges of phenotypes; thus, depending on its severity, this enzymopathy is classified from the mildest (Class IV) to the most severe (Class I). Therefore, understanding the correlation between the mutation sites of G6PD and the resulting phenotype greatly enhances the current knowledge of enzymopathies' phenotypic and genotypic heterogeneity, which will assist both clinical diagnoses and personalized treatments for patients with G6PD deficiency. In this review, we analyzed and compared the structural and functional data from 21 characterized G6PD variants found in the Mexican population that we previously characterized. In order to contribute to the knowledge regarding the function and structure of the variants associated with G6PD deficiency, this review aimed to determine the molecular basis of G6PD and identify how these mutations could impact the structure, stability, and function of the enzyme and its relation with the clinical manifestations of this disease.