Evaluation of Three Mutations in Codon 385 of Glucose-6-Phosphate Dehydrogenase via Biochemical and In Silico Analysis.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an enzymopathy that affects approximately 500 million people worldwide. A great number of mutations in the gene have been described. However, three class A G6PD variants known as G6PD Tomah (C385R), G6PD Kangnam (C385G), and G6PD Madrid (C385W) have been reported to be clinically important due to their associations with severe clinical manifestations such as hemolytic anemia.

Imidazole Carbamates as a Promising Alternative for Treating Trichomoniasis: In Vitro Effects on the Growth and Gene Expression of .

Metronidazole (MTZ) is the most common drug used against () infections; however, treatment failures and high rates of recurrence of trichomoniasis have been reported, suggesting the presence of resistance in to MTZ. Therefore, research into new therapeutic options against infections has become increasingly urgent. This study investigated the trichomonacidal activity of a series of five imidazole carbamate compounds (AGR-1, AGR-2, AGR-3, AGR-4, and AGR-5) through in vitro susceptibility assays to determine the IC value of each compound.

Identification of Hypoglycemic Glycolipids from by Affinity-Directed Fractionation, In Vitro, In Silico and Dynamic Light Scattering Analysis.

In the pursuit of identifying the novel resin glycoside modulators glucose-6-phosphatase and -glucosidase enzymes, associated with blood sugar regulation, methanol-soluble extracts from the flowers of (cazahuate, Nahuatl), renowned for its abundance of glycolipids, were employed. The methanol-soluble extracts were fractionated by applying the affinity-directed method with glucose-6-phosphatase enzymes from a rat's liver and -glucosidase enzymes from its intestines. Mass spectrometry and nuclear magnetic resonance were employed to identify the high-affinity compound as a free ligand following the release from the enzymatic complex.

Immunological Cross-Reactivity and Preclinical Assessment of a Colombian Anticoral Antivenom against the Venoms of Three Species.

Snakebite accident treatment requires the administration of antivenoms that provide efficacy and effectiveness against several snake venoms of the same genus or family. The low number of immunogenic components in venom mixtures that allow the production of antivenoms consequently gives them partial neutralization and a suboptimal pharmacological response. This study evaluates the immunorecognition and neutralizing efficacy of the polyvalent anticoral antivenom from the Instituto Nacional de Salud (INS) of Colombia against the heterologous endemic venoms of , and , and by assessing immunoreactivity through affinity chromatography, ELISA, Western blot, and neutralization capability.

Fused Enzyme Glucose-6-Phosphate Dehydrogenase::6-Phosphogluconolactonase (G6PD::6PGL) as a Potential Drug Target in , , and .

Several microaerophilic parasites such as , , and 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.

Structural, biochemical and immunochemical characterization of an acidic phospholipase A2 from Lachesis acrochorda (Viperidae: Crotalinae) venom.

Viperids of the genus Lachesis, also known as bushmasters, are capable of injecting great amounts of venom that cause severe envenomation incidents. Since phospholipases type A are mainly involved in edema and myonecrosis within the snakebite sites, in this work, the isolation, amino acid sequence and biochemical characterization of the first phospholipase type A from the venom of Lachesis acrochorda, named Lacro_PLA, is described. Lacro_PLA is an acidic aspartic 49 calcium-dependent phospholipase A with 93% similarity to the L.

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.

Nitazoxanide Inhibits the Bifunctional Enzyme GlG6PD::6PGL of : Biochemical and In Silico Characterization of a New Druggable Target.

Giardiasis, which is caused by infection, is a relevant cause of morbidity and mortality worldwide. Because no vaccines are currently available to treat giardiasis, chemotherapeutic drugs are the main options for controlling infection. Evidence has shown that the nitro drug nitazoxanide (NTZ) is a commonly prescribed treatment for giardiasis; however, the mechanisms underlying NTZ's antigiardial activity are not well-understood.

Phenolic Compounds from Wild Plant and Cultures of and Evaluation of Their Antioxidant Activity.

, is commonly used in traditional Mexican medicine. cultures were established from wild plant (WP) seeds, obtaining plant (IP), callus culture (CC), and cell suspension culture (CSC) with the objective to determine total phenol content (TPC) and flavonoids (TFC), as well as their antioxidant activity by DPPH, ABTS and TBARS assays, added to the compound's identification and quantification by HPLC, from methanol extracts obtained by sonication. CC showed significantly higher TPC and TFC than WP and IP, while CSC produced 2.

A subfraction obtained from the venom of the tarantula contains inhibitor cystine knot peptides and induces relaxation of rat aorta by inhibiting L-type voltage-gated calcium channels.

Venoms from tarantulas contain low molecular weight vasodilatory compounds whose biological action is conceived as part of the envenomation strategy due to its propagative effects. However, some properties of venom-induced vasodilation do not match those described by such compounds, suggesting that other toxins may cooperate with these ones to produce the observed biological effect. Owing to the distribution and function of voltage-gated ion channels in blood vessels, disulfide-rich peptides isolated from venoms of tarantulas could be conceived into potential vasodilatory compounds.

Pyridyl Methylsulfinyl Benzimidazole Derivatives as Promising Agents against and .

Protozoan parasites, such as and , cause the most prevalent infections in humans in developing countries and provoke significant morbidity and mortality in endemic countries. Despite its side-effects, metronidazole is still the drug of choice as a giardiacidal and trichomonacidal tissue-active agent. However, the emergence of metronidazole resistance and its evolved strategies of parasites to evade innate host defenses have hindered the identification and development of new therapeutic strategies against these parasites.

Chemical characterization of yellow-orange and purple varieties of Opuntia ficus-indica fruits and thermal stability of their betalains.

Betalains are plant pigments with biological properties and can be used instead of synthetic colorants to confer color and functional properties to foods. The objective of this work was to carry out the chemical characterization of two varieties of prickly pear of Opuntia ficus-indica, one of yellow-orange coloration (Mandarina) and the other of purple coloration (Vigor), through measurements of chemical parameters and color in pulp, antioxidant activity, total phenolic compounds, and betalain content. Considering the thermolability of betalains and their potential applications in food, the thermal stability and activation energy of betacyanins from Vigor variety and betaxanthins from the Mandarina variety were also evaluated and compared with those from beetroot, the main source of betalains.

Phytochemical Screening and Isolation of New -Clerodane Diterpenoids from Lotsy.

Phytochemical screening of an ethanol-water extract (EWE) from the bark of led to the isolation and identification of eight compounds, among them: five -clerodane diterpenoids [junceic acid (), 6()-acetoxy-15,16-diepoxy--cleroda-3,13(16),14-trien-20-oic acid (crotoguatenoic acid A) (), 6()-hydroxyoxy-15,16-diepoxy--cleroda-3,13(16),14-trien-20-oic acid (crotoguatenoic acid B) (), formosin F (), bartsiifolic acid ()], and three flavonoids [rutin (), epicatechin (), and quercetin ()]. Of these, and are reported here for the first time. Structures were established through conventional spectroscopy methods and their absolute configurations were determined by optical rotation and comparison of experimental electronic circular dichroism (ECD) and theoretical calculated ECD spectra.

G6PD::6PGL Fused Protein Inhibitors Decrease Trophozoite Viability: A New Alternative against Giardiasis.

Treatments to combat giardiasis have been reported to have several drawbacks, partly due to the drug resistance and toxicity of current antiparasitic agents. These constraints have prompted many researchers to investigate new drugs that act against protozoan parasites. Enzyme inhibition is an important means of regulating pathogen metabolism and has recently been identified as a significant alternative target in the search for new treatments.

TFEB; Beyond Its Role as an Autophagy and Lysosomes Regulator.

Transcription factor EB (TFEB) is considered the master transcriptional regulator of autophagy and lysosomal biogenesis, which regulates target gene expression through binding to CLEAR motifs. TFEB dysregulation has been linked to the development of numerous pathological conditions; however, several other lines of evidence show that TFEB might be a point of convergence of diverse signaling pathways and might therefore modulate other important biological processes such as cellular senescence, DNA repair, ER stress, carbohydrates, and lipid metabolism and WNT signaling-related processes. The regulation of TFEB occurs predominantly at the post-translational level, including phosphorylation, acetylation, SUMOylating, PARsylation, and glycosylation.

Biochemical and Kinetic Characterization of the Glucose-6-Phosphate Dehydrogenase from Strain 29CaP.

() has been proposed as the foremost risk factor for the development of gastric cancer. We found that express the enzyme glucose-6-phosphate dehydrogenase (HpG6PD), which participates in glucose metabolism via the pentose phosphate pathway. Thus, we hypothesized that if the biochemical and physicochemical characteristics of HpG6PD contrast with the host G6PD (human G6PD, HsG6PD), HpG6PD becomes a potential target for novel drugs against .

A Sea Anemone Venom Fraction Decreases Boar Sperm Cells Capacitation: Possible Involvement of HVA Calcium Channels.

Sea anemones produce venoms characterized by a complex mixture of low molecular weight compounds, proteins and peptides acting on voltage-gated ion channels. Mammal sperm cells, like neurons, are characterized by their ion channels. Calcium channels seem to be implicated in pivotal roles such as motility and capacitation.

The Role of Mass Spectrometry in the Discovery of Antibiotics and Bacterial Resistance Mechanisms: Proteomics and Metabolomics Approaches.

The abuse and incorrect administration of antibiotics has resulted in an increased proliferation of bacteria that exhibit drug resistance. The emergence of resistant bacteria has become one of the biggest health concerns globally, and an enormous effort has been made to combat them. However, despite the efforts, the emergence of resistant strains is rapidly increasing, while the discovery of new classes of antibiotics has lagged.

Kinetic and Molecular Docking Studies to Determine the Effect of Inhibitors on the Activity and Structure of Fused G6PD::6PGL Protein from .

Trichomoniasis is a sexually transmitted disease with a high incidence worldwide, affecting 270 million people. Despite the existence of a catalog of available drugs to combat this infection, their extensive use promotes the appearance of resistant (), and some side effects in treated people, which are reasons why it is necessary to find new alternatives to combat this infection. In this study, we investigated the impact of an in-house library comprising 55 compounds on the activity of the fused G6PD::6PGL (TvG6PD::6PGL) protein, a protein mediating the first reaction step of the pentose phosphate pathway (PPP), a crucial pathway involved in the parasite's energy production.

Chemical structure of three basic Asp-49 phospholipases A2 isolated from Crotalus molossus nigrescens venom with cytotoxic activity against cancer cells.

Snake venoms are complex mixtures of molecules with several biological activities. Among these molecules, the enzymes with phospholipase A activity have been extensively studied in the venoms from snakes because of their importance in the envenomation process and symptoms. The Mexican rattlesnake Crotalus molossus nigrescens is widely distributed in the Mexican plateau.

Effects of High Dietary Carbohydrate and Lipid Intake on the Lifespan of .

Health and lifespan are influenced by dietary nutrients, whose balance is dependent on the supply or demand of each organism. Many studies have shown that an increased carbohydrate-lipid intake plays a critical role in metabolic dysregulation, which impacts longevity. has been successfully used as an in vivo model to study the effects of several factors, such as genetic, environmental, diet, and lifestyle factors, on the molecular mechanisms that have been linked to healthspan, lifespan, and the aging process.

Glucose-6-Phosphate Dehydrogenase::6-Phosphogluconolactonase from the Parasite . A Molecular and Biochemical Perspective of a Fused Enzyme.

is a single-celled eukaryotic parasite with a small genome and is considered an early divergent eukaryote. The pentose phosphate pathway (PPP) plays an essential role in the oxidative stress defense of the parasite and the production of ribose-5-phosphate. In this parasite, the glucose-6-phosphate dehydrogenase (G6PD) is fused with the 6-phosphogluconolactonase (6PGL) enzyme, generating the enzyme named G6PD::6PGL that catalyzes the first two steps of the PPP.

Glucose-6-Phosphatase and α-Glucosidase Inhibitors from Roots Identified by Affinity-Directed Fractionation.

Unlabelled: The ethanol/water-soluble extracts of the roots of M. Martens & Galeotti, Smilacaceae, which have been appreciated since pre-Hispanic times and traditionally used to treat type 2 diabetes in Mexico, were fractionated by the application of the affinity-directed method to identify glucose-6-phosphatase and α-glucosidase inhibitors. Mass spectrometry was used to identify the inhibitor as free ligands after released from the enzymatic complex by denaturing acidic conditions.

Novel inhibitors of human glucose-6-phosphate dehydrogenase (HsG6PD) affect the activity and stability of the protein.

Background: The pentose phosphate pathway (PPP) has received significant attention because of the role of NADPH and R-5-P in the maintenance of cancer cells, which are necessary for the synthesis of fatty acids and contribute to uncontrollable proliferation. The HsG6PD enzyme is the rate-limiting step in the oxidative branch of the PPP, leading to an increase in the expression levels in tumor cells; therefore, the protein has been proposed as a target for the development of new molecules for use in cancer.

Methods: Through in vitro studies, we assayed the effects of 55 chemical compounds against recombinant HsG6PD.