Tetrahydrofolate biosynthesis and distribution in higher plants

2005 ◽  
Vol 33 (4) ◽  
pp. 758-762 ◽  
Author(s):  
T. Sahr ◽  
S. Ravanel ◽  
F. Rébeillé
Keyword(s):  
Carbon Metabolism ◽  
Growth And Development ◽  
De Novo ◽  
Higher Plants ◽  
The Other ◽  
Transfer Reactions ◽  
Intracellular Traffic ◽  
Vitamin B9 ◽  
Carbon Transfer ◽  
One Carbon Metabolism

One-carbon transfer reactions are mediated by H4F (tetrahydrofolate), a soluble coenzyme (vitamin B9) that is synthesized de novo by plants and microorganisms, and absorbed from the diet by animals. H4F synthesis in plants is quartered between the plastids, the cytosol and the mitochondria, a spatial distribution that is not observed in the other organisms and that suggests a complex intracellular traffic. Also, the activity of H4F synthesis fluctuates during plant growth, depending on the tissue and the developmental stage of the seedling, thus illustrating the flexibility of one-carbon metabolism in these organisms. This paper will focus on our recent knowledge about H4F synthesis in the plant cell and will briefly describe the activity of the pathway during the growth and development of the seedling.

scholarly journals One-Carbon Metabolism in Fatty Liver Disease and Fibrosis: One-Carbon to Rule Them All

2020 ◽  
Vol 150 (5) ◽  
pp. 994-1003
Author(s):  
Robin P da Silva ◽  
Brandon J Eudy ◽  
Rafael Deminice
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Carbon Metabolism ◽  
Fatty Liver Disease ◽  
De Novo ◽  
Future Research ◽  
Excessive Alcohol Consumption ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Lipid ◽  
One Carbon Metabolism

ABSTRACT Nonalcoholic fatty liver disease (NAFLD) is a term used to characterize a range of disease states that involve the accumulation of fat in the liver but are not associated with excessive alcohol consumption. NAFLD is a prevalent disease that can progress to organ damage like liver cirrhosis and hepatocellular carcinoma. Many animal models have demonstrated that one-carbon metabolism is strongly associated with NAFLD. Phosphatidylcholine is an important phospholipid that affects hepatic lipid homeostasis and de novo synthesis of this phospholipid is associated with NAFLD. However, one-carbon metabolism serves to support all cellular methylation reactions and catabolism of methionine, serine, glycine, choline, betaine, tryptophan, and histidine. Several different pathways within one-carbon metabolism that play important roles in regulating energy metabolism and immune function have received less attention in the study of fatty liver disease and fibrosis. This review examines what we have learned about hepatic lipid metabolism and liver damage from the study of one-carbon metabolism thus far and highlights unexplored opportunities for future research.

The possible rôle of xanthoxin in plant growth and development

1978 ◽  
Vol 284 (1002) ◽  
pp. 499-507 ◽  
Keyword(s):  
Abscisic Acid ◽  
Hormonal Regulation ◽  
Growth And Development ◽  
Higher Plants ◽  
The Other ◽  
Regulatory Function ◽  
Root Tip ◽  
Root Tips ◽  
Root Primordia ◽  
Lateral Root Primordia

In higher plants, abscisic acid and xanthoxin are two potent growth regulators. Although similar properties in both substances have been demonstrated in several biological tests including biochemical interconversion of the substances, evidence is available that in the plant as a whole, xanthoxin has regulatory functions other than those of abscisic acid. Several environmental factors, such as water supply, photoperiod and low temperature, which affect growth and development also greatly change the level of abscisic acid in the plant; however, only small variations in the xanthoxin level have been observed in response to changes in the environmental conditions. On the other hand, a strong enhancement of the xanthoxin level can be induced when dark-grown seedlings are briefly illuminated; this treatment, however, has no influence on the abscisic acid level. This observation supports the hypothesis that light-induced inhibition of growth may be mediated by an increased formation of the growth inhibitor xanthoxin. Light-induced enhancement of the xanthoxin level may also contribute to the phototropic bending in dictyledonous seedlings. Evidence has been obtained from experiments in this laboratory that xanthoxin may be involved in the regulation of root branching. Decapitation of root tips causes a significant increase in the number of lateral root primordia. Chromatographic studies reveal the presence of two substances in the root, which, in a specific bioassay, are active inhibitors of the development of root primordia. The activity of these root inhibitors in the basal part decreases when the root tip is removed. They are probably produced in the root tip and are transported to the base. One of these inhibitors has been identified as xanthoxin, the other is cytokinin. The hormonal regulation of abscission is another process where xanthoxin may have a regulatory function. Senescent, abscinding petioles contain a factor called ‘senescence factor’ which promotes the abscission of leaves. In an attempt to identify its chemical nature, it was found that at least three different abscission accelerating substances, including xanthoxin, participate in the composition of the senescence factor.

scholarly journals Maternal One-carbon Metabolism during the Periconceptional Period and Human Foetal Brain Growth: A Systematic Review

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1634
Author(s):  
Eleonora Rubini ◽  
Inge M. M. Baijens ◽  
Alex Horánszky ◽  
Sam Schoenmakers ◽  
Kevin D. Sinclair ◽  
...  
Keyword(s):  
Carbon Metabolism ◽  
Growth And Development ◽  
Autism Spectrum ◽  
Head Size ◽  
Brain Growth ◽  
Foetal Head ◽  
Foetal Brain ◽  
Head Growth ◽  
Periconceptional Period ◽  
One Carbon Metabolism

The maternal environment during the periconceptional period influences foetal growth and development, in part, via epigenetic mechanisms moderated by one-carbon metabolic pathways. During embryonic development, one-carbon metabolism is involved in brain development and neural programming. Derangements in one-carbon metabolism increase (i) the short-term risk of embryonic neural tube-related defects and (ii) long-term childhood behaviour, cognition, and autism spectrum disorders. Here we investigate the association between maternal one-carbon metabolism and foetal and neonatal brain growth and development. Database searching resulted in 26 articles eligible for inclusion. Maternal vitamin B6, vitamin B12, homocysteine, and choline were not associated with foetal and/or neonatal head growth. First-trimester maternal plasma folate within the normal range (> 17 nmol/L) associated with increased foetal head size and head growth, and high erythrocyte folate (1538–1813 nmol/L) with increased cerebellar growth, whereas folate deficiency (< 7 nmol/L) associated with a reduced foetal brain volume. Preconceptional folic acid supplement use and specific dietary patterns (associated with increased B vitamins and low homocysteine) increased foetal head size. Although early pregnancy maternal folate appears to be the most independent predictor of foetal brain growth, there is insufficient data to confirm the link between maternal folate and offspring risks for neurodevelopmental diseases.

scholarly journals SARS-CoV-2 hijacks folate and one-carbon metabolism for viral replication

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yuchen Zhang ◽  
Rui Guo ◽  
Sharon H. Kim ◽  
Hardik Shah ◽  
Shuting Zhang ◽  
...  
Keyword(s):  
Viral Replication ◽  
Carbon Metabolism ◽  
De Novo ◽  
Transcriptional Level ◽  
Viral Genomes ◽  
Infected Cells ◽  
One Carbon Metabolism ◽  
Viral Lifecycle ◽  
Host Metabolism ◽  
Intracellular Glucose

AbstractThe recently identified Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the cause of the COVID-19 pandemic. How this novel beta-coronavirus virus, and coronaviruses more generally, alter cellular metabolism to support massive production of ~30 kB viral genomes and subgenomic viral RNAs remains largely unknown. To gain insights, transcriptional and metabolomic analyses are performed 8 hours after SARS-CoV-2 infection, an early timepoint where the viral lifecycle is completed but prior to overt effects on host cell growth or survival. Here, we show that SARS-CoV-2 remodels host folate and one-carbon metabolism at the post-transcriptional level to support de novo purine synthesis, bypassing viral shutoff of host translation. Intracellular glucose and folate are depleted in SARS-CoV-2-infected cells, and viral replication is exquisitely sensitive to inhibitors of folate and one-carbon metabolism, notably methotrexate. Host metabolism targeted therapy could add to the armamentarium against future coronavirus outbreaks.

scholarly journals Serine and one-carbon metabolisms bring new therapeutic venues in prostate cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Carlo Ganini ◽  
Ivano Amelio ◽  
Riccardo Bertolo ◽  
Eleonora Candi ◽  
Angela Cappello ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Carbon Metabolism ◽  
Potential Role ◽  
De Novo ◽  
Cancer Pathogenesis ◽  
Gene And Protein Expression ◽  
Serine Pathway ◽  
One Carbon Metabolism ◽  
Serine Metabolism

AbstractSerine and one-carbon unit metabolisms are essential biochemical pathways implicated in fundamental cellular functions such as proliferation, biosynthesis of important anabolic precursors and in general for the availability of methyl groups. These two distinct but interacting pathways are now becoming crucial in cancer, the de novo cytosolic serine pathway and the mitochondrial one-carbon metabolism. Apart from their role in physiological conditions, such as epithelial proliferation, the serine metabolism alterations are associated to several highly neoplastic proliferative pathologies. Accordingly, prostate cancer shows a deep rearrangement of its metabolism, driven by the dependency from the androgenic stimulus. Several new experimental evidence describes the role of a few of the enzymes involved in the serine metabolism in prostate cancer pathogenesis. The aim of this study is to analyze gene and protein expression data publicly available from large cancer specimens dataset, in order to further dissect the potential role of the abovementioned metabolism in the complex reshaping of the anabolic environment in this kind of neoplasm. The data suggest a potential role as biomarkers as well as in cancer therapy for the genes (and enzymes) belonging to the one-carbon metabolism in the context of prostatic cancer.

Association of upregulation of serine and one carbon metabolism genes with shorter recurrence-free and overall survival in urothelial bladder cancer (UBC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 477-477
Author(s):  
Michael Lattanzi ◽  
Michael Pacold ◽  
Arjun Vasant Balar
Keyword(s):  
Bladder Cancer ◽  
Carbon Metabolism ◽  
De Novo ◽  
Univariate Analysis ◽  
The Cancer Genome Atlas ◽  
Expression Data ◽  
Key Enzyme ◽  
One Carbon Metabolism ◽  
Muscle Invasive

477 Background: Antimetabolites (e.g. methotrexate and gemcitabine) are not frequently used in the treatment of most solid tumors, but are effective in the treatment of UBC. Rapid cancer cell proliferation relies on an abundance of serine-derived one carbon units to support macromolecule synthesis. Specifically, PHGDH, which encodes a key enzyme of de novo serine synthesis, is amplified in breast cancer and in melanoma, and small molecule inhibitors of enzymes in this pathway are in early clinical development. However, the enzymes of serine and one carbon metabolism have not been widely investigated in UBC. Methods: We conducted an observational analysis of The Cancer Genome Atlas UBC cohort, focusing on gene expression data from a targeted panel indicated by Yang, et al. to be involved in serine and one carbon metabolism. Univariate Cox proportional hazard models were utilized to identify genes impacting OS and RFS, and a subsequent multivariate model was employed to control for inter-gene associations. Results: Expression data from 14 genes were analyzed among 436 UBC patients, of whom complete data were available for 422. At a median follow-up of 17 months, 188 of 422 patients had died. On univariate analysis, 7 of 14 genes were significantly associated with OS: PHGDH, PSPH, MTHFD1, MTHFD2, MTHFD1L, MTHFD2L, and ALDH1L2 (all P < 0.05). Interestingly, overexpression was associated with worse OS for all but one gene, MTHFD2L (HR 0.74), which is known to be underexpressed by cancer cells in favor of MTHFD2 (HR 1.21). In multivariate analysis, overexpression of PHGDH (HR 1.19, P = 0.008), MTHFD1 (HR 1.33, P = 0.041), and ALDH1L2 (HR 1.21, P < 0.001) were independent predictors of poor survival. RFS analysis was limited by missing data; nevertheless, univariate analyses found MTHFD1, MTHFD2, MTHFD1L, MTHFD2L, and ALDH1L2 to be associated with RFS (all P < 0.05). Conclusions: Within the limits of this observational study, these data suggest that serine and one carbon metabolism is important in the progression and prognosis of muscle-invasive bladder cancer. Subsequent in vitro analyses are needed to validate the prognostic and therapeutic significance of these findings.

scholarly journals Multifaceted role of one-carbon metabolism on immunometabolic control and growth during pregnancy, lactation and the neonatal period in dairy cattle

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Danielle N. Coleman ◽  
Abdulrahman S. Alharthi ◽  
Yusheng Liang ◽  
Matheus Gomes Lopes ◽  
Vincenzo Lopreiato ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dairy Cattle ◽  
Carbon Metabolism ◽  
Growth And Development ◽  
Immune Dysfunction ◽  
Production Performance ◽  
Methyl Donors ◽  
Methyl Donor ◽  
One Carbon Metabolism ◽  
And Oxidative Stress

AbstractDairy cattle undergo dramatic metabolic, endocrine, physiologic and immune changes during the peripartal period largely due to combined increases in energy requirements for fetal growth and development, milk production, and decreased dry matter intake. The negative nutrient balance that develops results in body fat mobilization, subsequently leading to triacylglycerol (TAG) accumulation in the liver along with reductions in liver function, immune dysfunction and a state of inflammation and oxidative stress. Mobilization of muscle and gluconeogenesis are also enhanced, while intake of vitamins and minerals is decreased, contributing to metabolic and immune dysfunction and oxidative stress. Enhancing post-ruminal supply of methyl donors is one approach that may improve immunometabolism and production synergistically in peripartal cows. At the cellular level, methyl donors (e.g. methionine, choline, betaine and folic acid) interact through one-carbon metabolism to modulate metabolism, immune responses and epigenetic events. By modulating those pathways, methyl donors may help increase the export of very low-density lipoproteins to reduce liver TAG and contribute to antioxidant synthesis to alleviate oxidative stress. Thus, altering one-carbon metabolism through methyl donor supplementation is a viable option to modulate immunometabolism during the peripartal period. This review explores available data on the regulation of one-carbon metabolism pathways in dairy cows in the context of enzyme regulation, cellular sensors and signaling mechanisms that might respond to increased dietary supply of specific methyl donors. Effects of methyl donors beyond the one-carbon metabolism pathways, including production performance, immune cell function, mechanistic target or rapamycin signaling, and fatty acid oxidation will also be highlighted. Furthermore, the effects of body condition and feeding system (total mixed ration vs. pasture) on one-carbon metabolism pathways are explored. Potential effects of methyl donor supply during the pepartum period on dairy calf growth and development also are discussed. Lastly, practical nutritional recommendations related to methyl donor metabolism during the peripartal period are presented. Nutritional management during the peripartal period is a fertile area of research, hence, underscoring the importance for developing a systems understanding of the potential immunometabolic role that dietary methyl donors play during this period to promote health and performance.

Polymorphisms in One-Carbon Metabolism Genes and Overall Survival in Diffuse Large B-Cell Lymphoma (DLBCL).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1568-1568
Author(s):  
James R. Cerhan ◽  
Matthew J. Maurer ◽  
Patricia Hartge ◽  
Stephen J. Chanock ◽  
Thomas M. Habermann ◽  
...  
Keyword(s):  
Overall Survival ◽  
Genetic Variation ◽  
Risk Score ◽  
Carbon Metabolism ◽  
B Cell Lymphoma ◽  
Clinical Variables ◽  
Carbon Transfer ◽  
One Carbon Metabolism ◽  
The Impact

Abstract Background. Intracellular one-carbon transfer reactions are essential for nucleotide synthesis and methylation of biologic compounds including DNA. Previous studies have linked genetic variants in one-carbon metabolism genes with risk of developing NHL, but little is known regarding the impact of these variants on disease outcome. We evaluated the hypothesis that inherited genetic variation in genes involved in one-carbon metabolism is associated with overall survival in DLBCL. Methods. We genotyped 30 single nucleotide polymorphisms (SNPs) from 18 candidate one-carbon metabolism genes in 215 DLBCL patients who participated in a population-based case-control study conducted from 1998–2000 using the SEER (Surveillance, Epidemiology and End Results) cancer registries in the Detroit, Iowa, Los Angeles and Seattle. Stage, B-symptoms, first course of therapy, date of last follow-up and vital status through early 2005 were obtained from cancer registry files. Cox proportional hazards analysis was used to estimate hazard ratios (HR) and corresponding 95% confidence intervals for the association between individual SNPs and overall survival, adjusting for age, demographic and clinical factors. We also used parallel modeling strategies to identify the best summary multi-SNP risk score to predict survival. Results. The median age at diagnosis was 57 years (range, 20–74), and 50 (23%) of the patients died during follow-up, with a median follow-up of 57 months (range, 31–78 months) for surviving patients. After adjusting for demographic and clinical variables, SNPs in SHMT1 (rs1979276; HRCT/TT=2.47, 1.31–4.67), BHMT (rs585800; HRAT/TT=2.02, 1.16–3.54), and TCN1 (rs526934; HRTT=1.86, 1.04–3.33) were the strongest and most robust predictors of survival. A summary score of the number of deleterious genotypes (0–3) from these three genes was strongly associated with survival (p=7.9 x 10−5) after accounting for demographic and clinical variables (HR=2.58 per deleterious genotype, 95% CI 1.75–3.80). A risk score combining the three SNPs with clinical and demographic variables (score of 0 to 5) was even more strongly associated with survival (p=1.4 x 10−13); the Kaplan Meier survival curves are shown in the Figure. In a time-dependent ROC analysis, the combined risk score had a concordance index of 0.75 at 5 years of follow-up (95% CI 0.69–0.81). Conclusion: Host genetic variation in the one-carbon metabolism genes SHMT1, BHMT, and TCN1, individually and particularly in combination, was associated with overall DLBCL survival after accounting for clinical and demographic factors, supporting a role for this pathway in disease progression. Future work should evaluate interactions of genes from this pathway with dietary nutrients and therapeutic agents in DLBCL prognosis. Figure Figure

Canadian Society of Plant Physiologists Gold Medal Review / Synthèse médaillée d'or de la Société canadienne physiologie végétaleThe fascinating world of folate and one-carbon metabolism

2000 ◽  
Vol 78 (6) ◽  
pp. 691-708 ◽  
Author(s):  
Edwin A Cossins
Keyword(s):  
Carbon Metabolism ◽  
De Novo ◽  
Normal Growth ◽  
Gold Medal ◽  
Animal Cells ◽  
Isolation And Characterization ◽  
Folate Biosynthesis ◽  
One Carbon Metabolism ◽  
Société Canadienne ◽  
Antifolate Drugs

Folate was first isolated from spinach leaves in 1941 and characterized as pteroylglutamic acid. Although plants, fungi, and bacteria synthesize folate de novo, animal cells lack key enzymes of the folate biosynthetic pathway and a dietary source of folate is required for normal growth and development. Folates have importance in human nutrition, health, and disease, and antifolate drugs are commonly used in cancer chemotherapy. In the majority of living cells folates occur as one-carbon substituted tetrahydropteroylpolyglutamate derivatives. These folates donate one-carbon groups during the synthesis of purines, formylmethionyl-tRNA, thymidylate, serine, and methionine. In the last 30 years, research on the folate biochemistry of plant species has intensified and been aided by the development of improved methods for folate isolation and characterization. These studies have resulted in basic information on the nature of plant folylpolyglutamates, folate biosynthesis, the enzymology of several folate-dependent reactions, and the roles of chloroplasts, mitochondria, and the cytosol in the pathways of one-carbon metabolism.Key words: plants, folates, folate biosynthesis, folate-dependent enzymes, one-carbon metabolism.

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