Role of Folate and Folic Acid During Pregnancy

Pregnancy represents a period of fast tissue growth of maternal and foetal tissues that's related to enhanced energy and nutrient needs. Maternal nutrition throughout gestation period, has being essential for best offspring development, reducing long unwellness burden and for general health throughout life. Maternal Folate throughout pregnancy might have numerous roles in offspring health, as well as neurodevelopment and psychological feature performance in childhood. Folate is crucial for C1 metabolism, a network of pathways concerned in many biological processes as well as nucleotide synthesis, deoxyribonucleic acid repair and methylation reactions. The periconceptional use of pteroylglutamic acid (Folic Acid ) containing supplements reduces the primary incidence, as well as recurrence of neural tube defects. Folic Acid (FA) are artificial form of a necessary vitamin generically considered Folates or B9. It is concerned in one-carbon metabolism, and it's been connected to lowering neural tube Defect (NTD). National programs to mandate fortification of food with Folic Acid have reduced the prevalence of NTDs worldwide . The indisputable protecting role of Folic Acid in the hindrance of NTD, in addition to the low compliance of women to Folic Acid recommendations, has aroused the choice of mandatory Folic Acid fortification, a policy currently in place in over eighty countries worldwide. Mandatory food fortification needs food makers to feature Folic Acid to certain foods (e.g. starch or grain products), whereas voluntary fortification permits Folic Acid to be added to foods at the discretion of manufacturers. Food fortification with Folic Acid because the intervention is likely to achieve increasing Folic Acid intake among populations throughout the world. The objective of this article is to discuss the Role of Folic Acid and Folate during pregnancy and to review the role of Folate and Folic Acid , metabolism , absorption and Folic Acid effects on maternal on the basis of recent findings that are important for implementation of fortified food to design future studies. Keywords: Neurodevelopment, Methylation Reactions, Pteroylglutamic Acid, Bioavailability, Monoglutamates.

Folate Transport and One-Carbon Metabolism in Targeted Therapies of Epithelial Ovarian Cancer

New therapies are urgently needed for epithelial ovarian cancer (EOC), the most lethal gynecologic malignancy. To identify new approaches for targeting EOC, metabolic vulnerabilities must be discovered and strategies for the selective delivery of therapeutic agents must be established. Folate receptor (FR) α and the proton-coupled folate transporter (PCFT) are expressed in the majority of EOCs. FRβ is expressed on tumor-associated macrophages, a major infiltrating immune population in EOC. One-carbon (C1) metabolism is partitioned between the cytosol and mitochondria and is important for the synthesis of nucleotides, amino acids, glutathione, and other critical metabolites. Novel inhibitors are being developed with the potential for therapeutic targeting of tumors via FRs and the PCFT, as well as for inhibiting C1 metabolism. In this review, we summarize these exciting new developments in targeted therapies for both tumors and the tumor microenvironment in EOC.

Conserved Metabolic and Evolutionary Themes in Microbial Degradation of Carbamate Pesticides

Carbamate pesticides are widely used as insecticides, nematicides, acaricides, herbicides and fungicides in the agriculture, food and public health sector. However, only a minor fraction of the applied quantity reaches the target organisms. The majority of it persists in the environment, impacting the non-target biota, leading to ecological disturbance. The toxicity of these compounds to biota is mediated through cholinergic and non-cholinergic routes, thereby making their clean-up cardinal. Microbes, specifically bacteria, have adapted to the presence of these compounds by evolving degradation pathways and thus play a major role in their removal from the biosphere. Over the past few decades, various genetic, metabolic and biochemical analyses exploring carbamate degradation in bacteria have revealed certain conserved themes in metabolic pathways like the enzymatic hydrolysis of the carbamate ester or amide linkage, funnelling of aryl carbamates into respective dihydroxy aromatic intermediates, C1 metabolism and nitrogen assimilation. Further, genomic and functional analyses have provided insights on mechanisms like horizontal gene transfer and enzyme promiscuity, which drive the evolution of degradation phenotype. Compartmentalisation of metabolic pathway enzymes serves as an additional strategy that further aids in optimising the degradation efficiency. This review highlights and discusses the conclusions drawn from various analyses over the past few decades; and provides a comprehensive view of the environmental fate, toxicity, metabolic routes, related genes and enzymes as well as evolutionary mechanisms associated with the degradation of widely employed carbamate pesticides. Additionally, various strategies like application of consortia for efficient degradation, metabolic engineering and adaptive laboratory evolution, which aid in improvising remediation efficiency and overcoming the challenges associated with in situ bioremediation are discussed.

Photorespiration: The Futile Cycle?

Photorespiration, or C2 photosynthesis, is generally considered a futile cycle that potentially decreases photosynthetic carbon fixation by more than 25%. Nonetheless, many essential processes, such as nitrogen assimilation, C1 metabolism, and sulfur assimilation, depend on photorespiration. Most studies of photosynthetic and photorespiratory reactions are conducted with magnesium as the sole metal cofactor despite many of the enzymes involved in these reactions readily associating with manganese. Indeed, when manganese is present, the energy efficiency of these reactions may improve. This review summarizes some commonly used methods to quantify photorespiration, outlines the influence of metal cofactors on photorespiratory enzymes, and discusses why photorespiration may not be as wasteful as previously believed.

Genomic Characterization and Distribution Pattern of a Novel Marine OM43 Phage

Bacteriophages have a significant impact on the structure and function of marine microbial communities. Phages of some major bacterial lineages have recently been shown to dominate the marine viral communities. However, phages that infect many important bacterial clades still remained unexplored. Members of the marine OM43 clade are methylotrophs that play important roles in C1 metabolism. OM43 phages (phages that infect the OM43 bacteria) represent an understudied viral group with only one known isolate. In this study, we describe the genomic characterization and biogeography of an OM43 phage that infects the strain HTCC2181, designated MEP301. MEP301 has a genome size of 34,774 bp. We found that MEP301 is genetically distinct from other known phage isolates and only displays significant sequence similarity with some metagenomic viral genomes (MVGs). A total of 12 MEP301-type MVGs were identified from metagenomic datasets. Comparative genomic and phylogenetic analyses revealed that MEP301-type phages can be separated into two subgroups (subgroup I and subgroup II). We also performed a metagenomic recruitment analysis to determine the relative abundance of reads mapped to these MEP301-type phages, which suggested that subgroup I MEP301-type phages are present predominantly in the cold upper waters with lower salinity. Notably, subgroup II phages have an inverse different distribution pattern, implying that they may infect hosts from a distinct OM43 subcluster. Our study has expanded the knowledge about the genomic diversity of marine OM43 phages and identified a new phage group that is widespread in the ocean.

Structure-based dynamic analysis of the glycine cleavage system suggests key residues for control of a key reaction step

Molecular shuttles play decisive roles in many multi-enzyme systems such as the glycine cleavage system (GCS) for one-carbon (C1) metabolism. In GCS, a lipoate swinging arm containing an aminomethyl moiety is attached to protein H and serves as a molecular shuttle among different proteins. Protection of the aminomethyl moiety in a cavity of protein H and its release induced by protein T are key processes but barely understood. Here, we present a detailed structure-based dynamic analysis of the induced release of the lipoate arm of protein H. Based on molecular dynamics simulations of interactions between proteins H and T, four major steps of the release process showing significantly different energy barriers and time scales can be distinguished. Mutations of a key residue, Ser-67 in protein H, led to a bidirectional tuning of the release process. This work opens ways to target C1 metabolism in biomedicine and the utilization of formate and CO2 for biosynthesis.

Comparative Proteomic Analysis of Leaves at Different Ages in Allotriploid Populus

Triploid poplar trees have been shown to have a number of growth advantages, especially much bigger leaves that contribute greatly to the increased biomass. In this study, we focused on the relationships between leaf age and leaf metabolism in triploids. We performed comparative proteomic analysis of the 5th (FDR5), 10th (FDR10), and 25th (FDR25) leaves from the apical meristems in allotriploids originated from first-division restitution (FDR). A total of 1970, 1916, and 1850 proteins were identified in the FDR5, FDR10, and FDR25, respectively. Principle component analysis (PCA) and differentially accumulated protein (DAP) analysis showed that FDR10 and FDR25 displayed higher similarities of protein accumulation patterns as compared to FDR5. MapMan enrichment analysis showed that several primary metabolic pathways or processes were significantly enriched in the DAPs. For example, photosynthesis, major CHO metabolism, glycolysis, N metabolism, redox, C1-metabolism, DNA, and protein turnover were significantly altered in both FDR10 and FDR25 compared with FDR5. In addition, amino acid metabolism and gluconeogenesis/glyoxylate cycle also underwent significant changes in FDR25 compared with FDR5. However, only amino acid metabolism was significantly enriched in the DAPs between FDR25 and FDR10. Further, DAP accumulation pattern analysis implied that FDR5, FDR10, and FDR25 were placed in the young, mature, and primary senescence stages of leaves. The most DAPs involved in the light reaction, photorespiration, Calvin cycle, starch and sucrose metabolism, pentose phosphate pathway (OPP), tricarboxylic acid (TCA) cycle, N metabolism, and C1-metabolism displayed higher accumulation in both FDR10 and FDR25 compared to FDR5. However, the most DAPs that are involved in cell wall and lipid metabolism, tetrapyrrole synthesis, nucleotide metabolism exhibited lower accumulation in both FDR10 and FDR25. Almost all DAPs between FDR-10 and FDR-25 showed a dramatic decrease in FDR25. KEGG enrichment analysis showed that carbon metabolism was altered significantly at different leaf ages. DAPs that are involved in carbon metabolism were predicted as different points in protein–protein interaction (PPI) networks from the STRING database. Finally, inconsistent transcript and protein abundance was found for DAPs, indicating the presence of posttranscriptional regulation during leaf-age progression process.

Lanthanide rarity in natural waters: implications for microbial C1 metabolism

ABSTRACT Research in the last decade has illuminated the important role that lanthanides play in microbial carbon metabolism, particularly methylotrophy. Environmental omics studies have revealed that lanthoenzymes are dominant in some environments, and laboratory studies have shown that lanthoenzymes are favored over their calcium-containing counterparts even when calcium is far more abundant. Lanthanide elements are common in rocks but occur at exceedingly low levels in most natural waters (picomolar to nanomolar range) with the exception of volcanic hot springs, which can reach micromolar concentrations. Calcium is orders of magnitude higher in abundance than lanthanide elements across natural settings. Bacteria that use lanthanides for growth on simple carbon compounds (e.g. methanol and ethanol) grow optimally at micromolar concentrations. It is highly likely that bacteria in the environment have evolved specialized lanthanide sequestration and high-affinity uptake systems to overcome lanthanide deprivation. Indeed, we identified genes in soil metagenomes encoding the lanthanide-binding protein lanmodulin, which may be important for cellular differentiation between calcium and lanthanides. More research is needed on microbial adaptations to lanthanide scarcity.

Metabolomic and transcriptomic signatures of prenatal excessive methionine support nature rather than nurture in schizophrenia pathogenesis

The imbalance of prenatal micronutrients may perturb one-carbon (C1) metabolism and increase the risk for neuropsychiatric disorders. Prenatal excessive methionine (MET) produces in mice behavioral phenotypes reminiscent of human schizophrenia. Whether in-utero programming or early life caregiving mediate these effects is, however, unknown. Here, we show that the behavioral deficits of MET are independent of the early life mother-infant interaction. We also show that MET produces in early life profound changes in the brain C1 pathway components as well as glutamate transmission, mitochondrial function, and lipid metabolism. Bioinformatics analysis integrating metabolomics and transcriptomic data reveal dysregulations of glutamate transmission and lipid metabolism, and identify perturbed pathways of methylation and redox reactions. Our transcriptomics Linkage analysis of MET mice and schizophrenia subjects reveals master genes involved in inflammation and myelination. Finally, we identify potential metabolites as early biomarkers for neurodevelopmental defects and suggest therapeutic targets for schizophrenia.