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Synthetic microbial community converts corn stover hydrolysate into high-purity L-lactic acid in the presence of fermentation inhibitors.

Lignocellulosic hydrolysates contain inhibitors that hinder lactic acid (LA) production. This study evaluated a synthetic microbial community (SMC) of five lactic acid bacteria for fermenting undetoxified corn stover hydrolysate. Metatranscriptome analysis revealed links between fermentation performance and inhibitor effects. Although LA yield decreased by 5.79% versus the control, SMC achieved 94.47% mixed sugar utilization and produced L-LA with 99.70% optical purity. Transcriptomic data suggest that hydrolysate inhibitors may suppress glycolysis and the pentose phosphate pathway, which may …

Metabolic Control of Immunity-Unveiling Neutrophil Mechanisms.

Immune metabolism is a central determinant of neutrophil development, plasticity, and function. Once considered strictly glycolytic, neutrophils are now recognized as metabolically flexible cells that dynamically engage glycolysis, the pentose phosphate pathway (PPP), amino acid metabolism, and lipid oxidation to meet energetic and biosynthetic demands. Neutrophil metabolism is tightly regulated by nutrient-sensing and stress-response pathways, including mTOR, AMPK, and HIF-1α, which integrate environmental cues such as hypoxia and nutrient deprivation. In disease, metabolic rewiring underlies…

Insights into the enzymatic mechanism of 6-phosphogluconolactonase from Trypanosoma brucei using structural data and molecular dynamics simulation.

Trypanosoma brucei is the causative agent of African sleeping sickness. Current work for the development of new drugs against this pathology includes evaluation of enzymes of the pentose phosphate pathway (PPP), which first requires a clear understanding of their function and mechanism of action. In this context, we focused on T. brucei 6-phosphogluconolactonase (Tb6PGL), which converts delta-6-phosphogluconolactone into 6-phosphogluconic acid in the second step of the PPP. We have determined the crystal structure of Tb6PGL in complex with two ligands, 6-phosphogluconic acid and citrate, at 2.…

New stable mutant (Gd(-) variants: G6PD Tashkent and G6PD Nucus. Molecular basis of hereditary enzyme deficiency.

This paper represents studies on the molecular basis of G6PD deficiency in erythrocytes of 4 hemizygote patients. In all cases G6PD deficien … total red cell population found immunologically was similar to the normal level. Stimulation of the pentose phosphate pathway (PPP) of G6PD Nucus erythrocytes insignificantly increased the rate of glucose consumption while in the case of G6PD Tashkent methylene blue raised the rate of PPP to half of the maximal rate of stimulated normal red cells.

Обзор метаболизма Олигодендроцита.

Олигодендроциты (ОИ) демонстрируют сложные метаболические взаимодействия, необходимые для нейрональной функции и здоровья CNS. В этой главе анализируется метаболизм ОН, в частности глюкозы, липидов и аминокислотного метаболизма, и их воздействие на синтез, техническое обслуживание и устойчивость CNS. ОН используют глюкозу для получения энергии с помощью гликолиза и пентоза фосфата, поддерживая производство СПС и антиоксидативную защиту. Липидный синтез, включая производство холестерина и финголипида, имеет решающее значение для поддержания целостности миелин и быстрого проведения сигнала. Кром

Совпадение в аннотации оригинала
Oligodendrocytes (OLs) exhibit complex metabolic interactions essential for neuronal function and CNS health. This chapter analyzes the meta … nthesis, maintenance, and CNS resilience. OLs utilize glucose for energy through glycolysis and the pentose phosphate pathway, supporting ATP production and antioxidative defenses. Lipid synthesis, including cholesterol and sphingolipid production, is critical for maintaining myelin integrity and rapid signal conduction. Furthermore, amino acid pathways, such as those invo …

Transcriptional and epigenetic basis for restoration of G6PD enzymatic activity in human G6PD-deficient cells.

HDAC inhibitors (HDACi) increase transcription of some genes through histone hyperacetylation. To test the hypothesis that HDACi-mediated enhanced transcription might be of therapeutic value for inherited enzyme deficiency disorders, we focused on the glycolytic and pentose phosphate pathways (GPPPs). We show that among the 16 genes of the GPPPs, HDACi selectively enhance transcription of glucose 6-phosphate dehydrogenase (G6PD). This requires enhanced recruitment of the generic transcription factor Sp1, with commensurate recruitment of histone acetyltransferases and deacetylases, increased hi…

The Role of Glucose Metabolism in Xenopus Primitive Myeloid Cell Development and Function.

Primitive Myeloid Cells (PMCs) arise from the anterior ventral blood islands during Xenopus laevis embryogenesis and migrate to colonize emb … y-specific inhibitors: 2-deoxy-D-glucose 2-DG (global glucose metabolism), YZ-9 (glycolysis), 6-AN (pentose phosphate pathway, PPP), and ST045849 (hexosamine biosynthetic pathway, HBP). The analyses showed that PMCs express high levels of glycolytic and ancillary metabolic enzymes. Global inhibition impaired PMC colonization and wound recruitment and modestly reduced the s …

Perspectives for new drugs against trypanosomiasis and leishmaniasis.

Diseases caused by pathogenic trypanosomatids cause great suffering throughout the developing world. New drugs for these diseases are urgent … s of two drug targets in trypanosomatids, 6-phosphogluconate dehydrogenase, the third enzyme of the pentose phosphate pathway, and dihydrofolate reductase, a key enzyme involved in DNA synthesis. Enzyme inhibitors can only be useful as drugs if they can enter cells and bind to their targets. Therefore we also discuss approaches to designing molecules that can specifically …

Hydrogen sulfide orchestrates compartmentalized carbon flux reprogramming to sustain NADPH-dependent redox homeostasis under salt stress in rice.

Hydrogen sulfide (H2S) is recognized as an important redox signaling molecule in plant stress responses, yet how it coordinates metabolic re … FBA activity and upstream metabolic enzymes, promoting glucose-6-phosphate flux into the oxidative pentose phosphate pathway and enhancing NADPH production to sustain redox buffering. Together, these findings reveal that H2S operates as a compartment-specific metabolic coordinator that integrates carbon metabolism with NADPH allocation, thereby enabling plants to prioriti …

An Optimized Dihydrodibenzothiazepine Lead Compound (SBI-0797750) as a Potent and Selective Inhibitor of Plasmodium falciparum and P. vivax Glucose 6-Phosphate Dehydrogenase 6-Phosphogluconolactonase.

In Plasmodium, the first two and rate-limiting enzymes of the pentose phosphate pathway, glucose 6-phosphate dehydrogenase (G6PD) and the 6-phosphogluconolactonase, are bifunctionally fused to a unique enzyme named GluPho, differing structurally and mechanistically from the respective human orthologs. Consistent with the enzyme's essentiality for malaria parasite proliferation and propagation, human G6PD deficiency has immense impact on protection against severe malaria, making PfGluPho an attractive antimalarial drug target. Herein we report on the optimized lead compound N-(((2R,4S)-1-cyclob…

6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 is essential for p53-null cancer cells.

The bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-4 (PFKFB4) controls metabolic flux through allosteric regulation of glycolysis. Here we show that p53 regulates the expression of PFKFB4 and that p53-deficient cancer cells are highly dependent on the function of this enzyme. We found that p53 downregulates PFKFB4 expression by binding to its promoter and mediating transcriptional repression via histone deacetylases. Depletion of PFKFB4 from p53-deficient cancer cells increased levels of the allosteric regulator fructose-2,6-bisphosphate, leading to increased glycolyti

Glucose-6-phosphate dehydrogenase deficiency: disadvantages and possible benefits.

We review here some recent data about Glucose-6-phosphate dehydrogenase (G6PD), the housekeeping X-linked gene encoding the first enzyme of the pentose phosphate pathway (PPP), a NADPH-producing dehydrogenase. This enzyme has been popular among clinicians, biochemists, geneticists and molecular biologists because it is the most common form of red blood cell enzymopathy. G6PD deficient erythrocytes do not generate NADPH in any other way than through the PPP and for this reason they are more susceptible than any other cells to oxidative damage. Moreover, this enzyme has also been of crucial impo…

Glucose-6-phosphate dehydrogenase--from oxidative stress to cellular functions and degenerative diseases.

Glucose-6-phosphate dehydrogenase (G6PD), the first and rate-limiting enzyme of the pentose phosphate pathway, is indispensable to maintenance of the cytosolic pool of NADPH and thus the cellular redox balance. The role of G6PD as an antioxidant enzyme has been recognized in erythrocytes for a long time, as its deficiency is associated with neonatal jaundice, drug- or infection-mediated hemolytic crisis, favism and, less commonly, chronic non-spherocytic hemolytic anemia. To a large extent, advances in the field were made on the pathophysiology of G6PD-deficient erythrocytes, and the molecular…

Histochemical studies of oxidoreductases in rat kidney regenerating after mercuric chloride injury.

The activities of succinic dehydrogenase, glucose-6-phosphate dehydrogenase, lactate dehydrogenase and cytochrome oxidase, representatives of the tricarboxylic acid cycle, pentose phosphate pathway, glycolysis and terminal oxidation, respectively, were investigated after necrosis induced with mercuric chloride. 24 hours after the administration of mercuric chloride, the activities of all four enzymes were decreased in the necrotic proximal tubular segments. By the third day of regeneration the activities had decreased or disappeared in all three portions of the necrotic proximal tubules as com…

Comparative study of erythrocyte glycolytic enzymes in man and in two species of Lagomorphae. (Ochotona rufescens rufescens and Oryctolagus cuniculus).

The authors made a comparative study of red cell enzyme glycolysis in man and in two species of Lagomorphae, the pika and the rabbit. The activities of the 12 enzymes of Embden-Meyerhoff pathway and of the two dehydrogenases of pentose shunt (glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase) were determined. Phosphoglycerate kinase and pyruvate kinase showed quite similar activities in pika erythrocytes and in erythrocytes from human umbilical cord. The levels of these enzymes differed significantly in the pika and in the rabbit. No differences were noted between pyruvate

Abnormalities of glucose and lipid metabolism in myocardial ischemia-reperfusion injury.

Myocardial ischemia-reperfusion injury is a common condition in cardiovascular diseases, and the mechanism of its occurrence involves multiple complex metabolic pathways and signaling pathways. Among these pathways, glucose metabolism and lipid metabolism play important roles in regulating myocardial energy metabolism. Therefore, this article focuses on the roles of glucose metabolism and lipid metabolism in myocardial ischemia-reperfusion injury, including glycolysis, glucose uptake and transport, glycogen metabolism and the pentose phosphate pathway; and triglyceride metabolism, fatty acid u…

Glycyrrhetinic Acid and Autocrine Motility Factor Converge on G6PD Suppression, Oxidative Stress, and Drug Retention to Impair Pancreatic Ductal Adenocarcinoma Cell Growth.

BACKGROUND/AIM: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, driven by chemoresistance and metabolic reprogramming centered on glucose-6-phosphate dehydrogenase (G6PD)-dependent pentose phosphate pathway activity. Exogenously administered autocrine motility factor (AMF) suppresses G6PD at transcriptional and protein levels, elevating intracellular reactive oxygen species (ROS) to cytostatic thresholds. Glycyrrhetinic acid (GA), a bioactive triterpenoid from licorice root, amplifies oxidative stress through mitochondrial membrane disruption, while concurr…

Skewing cPLA2α activity toward oxoeicosanoid production promotes neutrophil N2 polarization, wound healing, and the response to sepsis.

Uncontrolled inflammation is linked to poor outcomes in sepsis and wound healing, both of which proceed through distinct inflammatory and re … hrough the oxoeicosanoid receptor OXER1 and partially depended on OXER1-dependent inhibition of the pentose phosphate pathway (PPP). Thus, C1P binding to cPLA2α suppresses neutrophil N2 polarization, thereby impairing wound healing and the response to sepsis.

Conformational changes associated with cofactor/substrate binding of 6-phosphogluconate dehydrogenase from Escherichia coli and Klebsiella pneumoniae: Implications for enzyme mechanism.

6-Phosphogluconate dehydrogenase (6PGDH), the third enzyme of the pentose phosphate pathway, catalyzes the oxidative decarboxylation of 6-phosphogluconate, making ribulose 5-phosphate, along with the reduction of NADP(+) to NADPH and the release of CO(2). Here, we report the first apo-form crystal structure of the pathogenic Klebsiella pneumoniae 6PGDH (Kp6PGDH) and the structures of the highly homologous Escherichia coli K12 6PGDH (Ec6PGDH) complexed with substrate, substrate/NADPH and glucose at high resolution. The binding of NADPH to one subunit of the homodimeric structure triggered a 10 …

Diphenhydramine inhibits voltage-gated proton channels (Hv1) and induces acidification in leukemic Jurkat T cells- New insights into the pro-apoptotic effects of antihistaminic drugs.

An established characteristic of neoplastic cells is their metabolic reprogramming, known as the Warburg effect, with greater reliance on energetically less efficient pathways (such as glycolysis and pentose phosphate shunt) compared with oxidative phosphorylation. This results in an overproduction of acidic species that must be extruded to maintain intracellular homeostasis. We recently described that blocking the proton currents in leukemic cells mediated by Hv1 ion channels triggers a marked intracellular acidification and apoptosis induction. Moreover, histamine H1-receptor antagonists wer