The intestinal absorption of dietary folates in health and disease.

Ch, Halsted

doi:10.1080/07315724.1989.10720340

Cited by 45 publications

(27 citation statements)

References 44 publications

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“…In humans, most folate is consumed in the polyglutamyl form; however, folate is absorbed by tissue cells in the monoglutamyl form. Polyglutamyl folates are available for absorption and metabolic utilization only after enzymatic deconjugation in the small intestine by a mammalian deconjugase enzyme (11,29). In animal and human trials (7; A. MelseBoonstra, C. E. West, M. B. Katan, F. J. Kok, and P. Verhoef, submitted for publication), it has been reported that the bioavailability of monoglutamyl folate is higher than that of polyglutamyl folate.…”

Section: Discussionmentioning

confidence: 99%

ControlledModulation of Folate Polyglutamyl Tail Length by Metabolic Engineeringof Lactococcuslactis

Sybesma

Born

Starrenburg

et al. 2003

Appl Environ Microbiol

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The dairy starter bacterium Lactococcus lactis is able to synthesize folate and accumulates >90% of the produced folate intracellularly, predominantly in the polyglutamyl form. Approximately 10% of the produced folate is released into the environment. Overexpression of folC in L. lactis led to an increase in the length of the polyglutamyl tail from the predominant 4, 5, and 6 glutamate residues in wild-type cells to a maximum of 12 glutamate residues in the folate synthetase overproducer and resulted in a complete retention of folate in the cells. Overexpression of folKE, encoding the bifunctional protein 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase and GTP-cyclohydrolase I, resulted in reduction of the average polyglutamyl tail length, leading to enhanced excretion of folate. By simultaneous overexpression of folKE and folC, encoding the enzyme folate synthetase or polyglutamyl folate synthetase, the average polyglutamyl tail length was increased, again resulting in normal wild-type distribution of folate. The production of bioavailable monoglutamyl folate and almost complete release of folate from the bacterium was achieved by expressing the gene for ␥-glutamyl hydrolase from human or rat origin. These engineering studies clearly establish the role of the polyglutamyl tail length in intracellular retention of the folate produced. Also, the potential application of engineered food microbes producing folates with different tail lengths is discussed.

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Section: Discussionmentioning

confidence: 99%

ControlledModulation of Folate Polyglutamyl Tail Length by Metabolic Engineeringof Lactococcuslactis

Sybesma

Born

Starrenburg

et al. 2003

Appl Environ Microbiol

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“…Thus, diminished maternal bioavailability of folate may lead to neural-tube defects in their offspring. Halsted (1990) summarised studies from his group investigating the effect of gastrointestinal diseases on the absorption of 3 H-labelled folate and 14 C-labelled pteroylheptaglutamate. Absorption of folate and pteroylheptaglutamate was not affected by ulcerative colitis, but was diminished by tropical and coeliac sprue (Halsted, 1990).…”

Section: Host-related Factorsmentioning

confidence: 99%

“…Halsted (1990) summarised studies from his group investigating the effect of gastrointestinal diseases on the absorption of 3 H-labelled folate and 14 C-labelled pteroylheptaglutamate. Absorption of folate and pteroylheptaglutamate was not affected by ulcerative colitis, but was diminished by tropical and coeliac sprue (Halsted, 1990). The saturable folate transport system in the jejunum, and thus folate bioavailability, is pH dependent, with an acidic pH optimum (Halsted, 1979;Mason, 1990).…”

Section: Host-related Factorsmentioning

confidence: 99%

Bioavailability and bioefficacy of folate and folic acid in man

et al. 2001

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Folic acid is important because supplementation around the time of conception has been proven to lower the risk of having offspring with a neural-tube defect. Furthermore, both dietary folate and folic acid decrease plasma total homocysteine concentrations. Elevated plasma homocysteine concentrations are considered to be an independent risk factor for cardiovascular disease. The aim of the present review is to give an overview of factors influencing bioavailability and bioefficacy (the proportion of ingested nutrient converted to its active form) of food folate and folic acid, and to discuss the functional bioefficacy of folate and folic acid in decreasing plasma homocysteine concentrations. We use the mnemonic SLAMENGHI to group factors influencing bioavailability and bioefficacy: Species of folate; Linkage at molecular level; Amount of folate and folic acid consumed; Matrix; Effect modifiers; Nutrient status; Genetic factors; Host-related factors; mathematical Interactions between the various factors. Bioefficacy of folate from some foods is <50 % that of folic acid. This factor is most probably explained by the matrix factors, encapsulation and binding. However, often such effects cannot be distinguished from factors such as species, chain length of folate in food, effect modifiers and the amount of folate consumed in a meal. Folic acid provided as a supplement is well absorbed. However, the homocysteine-lowering capacity of doses of folic acid >500 g is limited. It is unclear whether unmetabolised folic acid poses health risks. This factor is of importance, because food fortification is now implemented in many countries and folic acid supplements are freely available. In particular circumstances host-related factors, such as gastrointestinal illness and pH of the jejunum, can influence

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“…The dietary folate in the form of folyl polyglutamates is hydrolyzed by folate hydrolase (prostate-specific membrane antigen) 1 (FOLH1) to folyl monoglutamates, which are absorbed easily by the intestinal cells (Halsted 1989). Folate reductase catalyzes the reduction of folate to dihydrofolate (DHF) and tetrahydrofolate (THF).…”

Section: Introductionmentioning

confidence: 99%

Population-level diversity in the association of genetic polymorphisms of one-carbon metabolism with breast cancer risk

et al. 2016

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Aberrations in one-carbon metabolism were reported to increase breast cancer risk by influencing the DNA synthesis and methylation of DNA and catecholamines. However, the results of these association studies remain inconclusive. We have explored the contribution of eight genetic polymorphisms in modulating the susceptibility to breast cancer by performing a meta-analysis of worldwide studies. In total, 62 case-control studies representing 17 different populations involving 18,117 breast cancer cases and 23,573 healthy controls were included in this meta-analysis. Out of the eight polymorphisms analyzed, methylenetetrahydrofolate reductase (MTHFR) C677T exhibited positive association with the breast cancer risk in both fixed effects (OR 1.14, 95 % CI 1.10-1.17) and random effects (OR 1.10, 95 % CI 1.02-1.18) models. Solute carrier family 19 (folate transporter), member 1 (SLC19A1) G80A exhibited positive association (OR 1.16, 95 % CI 1.03-1.31) while MTR A2756G exhibited an inverse association (OR 0.78, 95 % CI 0.75-0.82) with the breast in fixed effect model alone. Significant heterogeneity was observed in the association of MTHFR C677T with breast cancer even between studies from the same geographical area, specifically among Chinese, Indians, and Turks. Subgroup analysis revealed MTHFR C677T-mediated breast cancer risk in post-menopausal women and women with low dietary intake of folate. Geographical area wise segregation of data revealed MTHFR-mediated increased breast cancer risk in populations who consume methionine-rich diet. Altitude-level variations were observed in the association of SHMT1 C1420T with breast cancer. India and Brazil of same altitude showed an inverse association with this polymorphism, while USA and China that share similar altitude showed a null association. MTHFR C677T and SLC19A1 G80A are the two polymorphisms of one-carbon metabolic pathway that increase breast cancer in the worldwide population. Dietary patterns and altitudinal variations are the likely risk modulators that are contributing toward ethnic-and population-level variations in genetic associations.

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The intestinal absorption of dietary folates in health and disease.

Cited by 45 publications

References 44 publications

ControlledModulation of Folate Polyglutamyl Tail Length by Metabolic Engineeringof Lactococcuslactis

ControlledModulation of Folate Polyglutamyl Tail Length by Metabolic Engineeringof Lactococcuslactis

Bioavailability and bioefficacy of folate and folic acid in man

Population-level diversity in the association of genetic polymorphisms of one-carbon metabolism with breast cancer risk

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