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.

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.

scholarly journals Myo-inositol content in pteridophytes and the isolation and characterization of L-myo-inositol-1-phosphate synthase from Diplopterygium glaucum

2006 ◽  
Vol 18 (2) ◽  
pp. 291-298 ◽  
Author(s):  
D. R. Chhetri ◽  
A. K. Mukherjee ◽  
J. Adhikari
Keyword(s):  
De Novo ◽  
Deae Cellulose ◽  
Normal Growth ◽  
Apparent Molecular Weight ◽  
Life Forms ◽  
Partial Purification ◽  
Ph Optimum ◽  
Inositol 1 ◽  
Isolation And Characterization ◽  
Phosphate Synthase

Myo-inositol is involved in normal growth and development of all living organisms and L-myo-inositol-1-phosphate synthase (MIPS; EC: 5.5.1.4) is responsible for its de novo synthesis. This enzyme has been reported for a number of life forms including plants, animals and bacteria. In the present study free myo-inositol has been detected in the common pteridophytes found in the Darjeeling Himalayas and the enzyme, L-myo-inositol-1-phosphate synthase has been partially purified from Diplopterygium glaucum (Thunb.) Nakai. A crude homogenate from the reproductive pinnules of D. glaucum was subjected to streptomycin sulphate precipitation and 0-70% ammonium sulphate fractionation followed by successive chromatography through DEAE-cellulose, Hexylagarose and BioGel A-0.5m columns. This resulted in a partial purification of the enzyme of about 81-fold with 13.5% recovery. The pteridophytic MIPS specifically utilized D-glucose-6-phosphte and NAD+ as its substrate and co-factor, respectively. It shows a pH optimum between 7.0 and 7.5 while the temperature maximum was 30 °C. The enzyme activity was stimulated by NH4+, slightly inhibited by Na+, Ba2+ and Cd2+, and strongly inhibited by Li+, Zn2+ and Hg2+. EDTA, pCMB and some substrate isomers like glucose-1-phosphate, fructose-6-phosphte and galactose-6-phosphate were inhibitory to the enzyme. The apparent molecular weight of the native D. glaucum MIPS was determined to be approximately 171 kDa.

scholarly journals Isolation and characterization of mutants of the facultative methylotroph Arthrobacter P1 blocked in one-carbon metabolism

1987 ◽  
Vol 146 (4) ◽  
pp. 346-352 ◽  
Author(s):  
P. R. Levering ◽  
L. Tiesma ◽  
J. P. Woldendorp ◽  
M. Steensma ◽  
L. Dijkhuizen
Keyword(s):  
Carbon Metabolism ◽  
Arthrobacter P1 ◽  
Facultative Methylotroph ◽  
Isolation And Characterization ◽  
One Carbon Metabolism

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.

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 A hybrid stochastic model of folate-mediated one-carbon metabolism: Effect of the common C677T MTHFR variant on de novo thymidylate biosynthesis

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Karla Misselbeck ◽  
Luca Marchetti ◽  
Martha S. Field ◽  
Marco Scotti ◽  
Corrado Priami ◽  
...  
Keyword(s):  
Stochastic Model ◽  
Carbon Metabolism ◽  
De Novo ◽  
C677t Mthfr ◽  
The Common ◽  
One Carbon Metabolism

Genetic Variation: Impact on Folate (and Choline) Bioefficacy

2010 ◽  
Vol 80 (45) ◽  
pp. 319-329 ◽  
Author(s):  
Allyson A. West ◽  
Marie A. Caudill
Keyword(s):  
Carbon Metabolism ◽  
Genetic Variants ◽  
Plasma Homocysteine ◽  
Water Soluble ◽  
Gene Interactions ◽  
Dietary Folate ◽  
Methyl Donors ◽  
Common Genetic Variants ◽  
One Carbon Metabolism ◽  
The Impact

Folate and choline are water-soluble micronutrients that serve as methyl donors in the conversion of homocysteine to methionine. Inadequacy of these nutrients can disturb one-carbon metabolism as evidenced by alterations in circulating folate and/or plasma homocysteine. Among common genetic variants that reside in genes regulating folate absorptive and metabolic processes, homozygosity for the MTHFR 677C > T variant has consistently been shown to have robust effects on status markers. This paper will review the impact of genetic variants in folate-metabolizing genes on folate and choline bioefficacy. Nutrient-gene and gene-gene interactions will be considered along with the need to account for these genetic variants when updating dietary folate and choline recommendations.

Sign in / Sign up

Export Citation Format

Share Document