Equilibrium constants under physiological conditions for the condensation of acetaldehyde with tetrahydrofolic acid

Guynn, Robert W.; LaBaume, Linda B.; Henkin, Jack

doi:10.1016/0003-9861(82)90492-1

Cited by 7 publications

(3 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study we showed that L. reuteri produces a novel folate when cultured in acetate-containing media. This novel form was identified as 5,10-methenyl-THF with an additional methyl group, as detected by NMR and MS. Other studies also described the existence of noncanonical folates (39,40). Our results indicate that 5,10-methylmethylene-THF is produced by bacterial cells, suggesting that the mammalian microbiome may generate novel folate compounds.…”

Section: Discussionsupporting

confidence: 74%

“…Our results indicate that 5,10-methylmethylene-THF is produced by bacterial cells, suggesting that the mammalian microbiome may generate novel folate compounds. This novel folate is a substrate for the bacterial enzymes 5,10-methylene-THF reductase and 5,10-methylene-THF dehydrogenase (40,41). Furthermore, our studies indicate that commensal gut microbes such as L. reuteri can generate uncommon amino acids such as ethionine, and ethionine may promote new mechanisms of protein modification such as lysine ethylation.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Two‐carbon folate cycle of commensalLactobacillus reuteri6475 gives rise to immunomodulatory ethionine, a source for histone ethylation

Röth

Chiang

et al. 2018

FASEB j.

View full text Add to dashboard Cite

Colonization of the gut by certain probiotic Lactobacillus reuteri strains has been associated with reduced risk of inflammatory diseases and colorectal cancer. Previous studies pointed to a functional link between immunomodulation, histamine production, and folate metabolism, the central 1‐carbon pathway for the transfer of methyl groups. Using mass spectrometry and NMR spectroscopy, we analyzed folate metabolites of L. reuteri strain 6475 and discovered that the bacterium produces a 2‐carbon‐transporting folate in the form of 5, 10‐ethenyl‐tetrahydrofolyl polyglutamate. Isotopic labeling permitted us to trace the source of the 2‐carbon unit back to acetate of the culture medium. We show that the 2C folate cycle of L. reuteri is capable of transferring 2 carbon atoms to homocysteine to generate the unconventional amino acid ethionine, a known immunomodulator. When we treated monocytic THP‐1 cells with ethionine, their transcription of TNF‐α was inhibited and cell proliferation reduced. Mass spectrometry of THP‐1 histones revealed incorporation of ethionine instead of methionine into proteins, a reduction of histone‐methylation, and ethylation of histone lysine residues. Our findings suggest that the microbiome can expose the host to ethionine through a novel 2‐carbon transporting variant of the folate cycle and modify human chromatin via ethylation.—Roth, D., Chiang, A. J., Hu, W., Gugiu, G. B., Morra, C. N., Versalovic, J., Kalkum, M. The two‐carbon folate cycle of commensal Lactobacillus reuteri 6475 gives rise to immunomodulatory ethionine, a source for histone ethylation. FASEB J. 33,3536‐3548 (2019). http://www.fasebj.org

show abstract

Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Two‐carbon folate cycle of commensalLactobacillus reuteri6475 gives rise to immunomodulatory ethionine, a source for histone ethylation

Röth

Chiang

et al. 2018

FASEB j.

View full text Add to dashboard Cite

show abstract

“…However, the American Cancer Society Cancer Prevention Study II Nutrition Cohort has reported no association between folate intake and risk of breast cancer even among women who consumed alcohol (45). Alcohol may perturb folate metabolism through reducing intestinal absorption, increasing renal excretion (29), inhibiting methionine synthase in the liver (46,47), directly destroying folate (48), or interacting with tetrahydrofolate (46,49). In the Iowa Women's Health Study, the only published cohort study that has examined the interaction of folate intake, alcohol, and risk of breast cancer by hormone receptor status, there was no appreciable association with risk of ER + tumors at all levels of folate and alcohol, but there was an elevated risk of ER À tumors among women who had low intake of total folate and high intake of alcohol (50).…”

Section: Discussionmentioning

confidence: 99%

Folate Intake and Risk of Breast Cancer Characterized by Hormone Receptor Status

Zhang

Hankinson

Hunter

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

Folate plays an important role in DNA methylation, and aberrant methylation of the estrogen receptor (ER) gene may be related to the loss of ER gene expression in breast tumors. Thus, deficient folate status has been hypothesized to be associated primarily with ER gene -negative breast tumors, but data relating folate intake to breast cancer risk according to ER status are sparse. We conducted a prospective cohort analysis of folate intake among 88,744 women in the Nurses' Health Study who completed a food frequency questionnaire in 1980 and every 2 to 4 years thereafter.

show abstract

Folate and Cancer Chemoprevention

Zhang¹,

Willett²

2004

Cancer Chemoprevention

View full text Add to dashboard Cite

Equilibrium constants under physiological conditions for the condensation of acetaldehyde with tetrahydrofolic acid

Cited by 7 publications

References 21 publications

Two‐carbon folate cycle of commensalLactobacillus reuteri6475 gives rise to immunomodulatory ethionine, a source for histone ethylation

Two‐carbon folate cycle of commensalLactobacillus reuteri6475 gives rise to immunomodulatory ethionine, a source for histone ethylation

Folate Intake and Risk of Breast Cancer Characterized by Hormone Receptor Status

Folate and Cancer Chemoprevention

Contact Info

Product

Resources

About