The history of folic acid

Hoffbrand, A. V.; Weir, Donald G.

doi:10.1046/j.1365-2141.2001.02822.x

Cited by 139 publications

(94 citation statements)

References 84 publications

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“…For all crystallization experiments, equal volumes (150 nL or 1.0 μL) of protein or protein complex and each crystallant solution were combined. Conditions for crystallization were as follows: hFRα-P2 1 Tables S1 and S2. Data were collected on crystals flash frozen in liquid nitrogen via the oscillation method and were reduced using the HKL2000 program suite (72).…”

Section: Methodsmentioning

confidence: 99%

“…isothermal titration calorimetry | targeted drug delivery F olic acid, an essential vitamin developed in the 1940s for the treatment of anemia, is converted to functional, naturally occurring metabolites via the action of dihydrofolate reductase and hence can act as a dietary supplement for folates (1). Folates are necessary in eukaryotic cells for single carbon transfer reactions, notably the conversion of homocysteine to methionine and a multitude of steps in de novo nucleotide synthesis (2)(3)(4)(5).…”

mentioning

confidence: 99%

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Structures of human folate receptors reveal biological trafficking states and diversity in folate and antifolate recognition

Wibowo

Singh

Reeder

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

174

190

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Antifolates, folate analogs that inhibit vitamin B 9 (folic acid)-using cellular enzymes, have been used over several decades for the treatment of cancer and inflammatory diseases. Cellular uptake of the antifolates in clinical use occurs primarily via widely expressed facilitative membrane transporters. More recently, human folate receptors (FRs), high affinity receptors that transport folate via endocytosis, have been proposed as targets for the specific delivery of new classes of antifolates or folate conjugates to tumors or sites of inflammation. The development of specific, FR-targeted antifolates would be accelerated if additional biophysical data, particularly structural models of the receptors, were available. Here we describe six distinct crystallographic models that provide insight into biological trafficking of FRs and distinct binding modes of folate and antifolates to these receptors. From comparison of the structures, we delineate discrete structural conformations representative of key stages in the endocytic trafficking of FRs and propose models for pH-dependent conformational changes. Additionally, we describe the molecular details of human FR in complex with three clinically prevalent antifolates, pemetrexed (also Alimta), aminopterin, and methotrexate. On the whole, our data form the basis for rapid design and implementation of unique, FR-targeted, folate-based drugs for the treatment of cancer and inflammatory diseases.isothermal titration calorimetry | targeted drug delivery

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Structures of human folate receptors reveal biological trafficking states and diversity in folate and antifolate recognition

Wibowo

Singh

Reeder

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

174

190

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“…Folic acid (pteroyl-L-glutamic acid) is a water-soluble vitamin (vitamin B 9 ) found to be essential for numerous bodily functions [1]. As such, folic acid is not biologically active but the biological properties of the molecule relay upon its reduction to tetrahydrofolate and other related forms.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Surfactants-Assisted Folic Acid-Loaded Pectin Submicrospheres: Characterization and Hemocompatibility Assay

2016

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Folic acid is used for preventing and treating multiple diseases and disorders, administered in the form of oral supplements. The present research work was aimed to study the influence of two non-ionic surfactants Poloxamer and Tween 80 (Polysorbate 80) on pectin submicrospheres formulations. Typical natural polymer pectin was used to encapsulate folic acid by cross linking method. The resultant submicrospheres contributed to improve the aqueous solubility to enhance the bioavailability of folic acid. During investigation, it was observed that pectin polymers influenced kinetics of the rate of reaction more intensively than the surfactants. The physical phenomenon caused the change in their size, shape and chemistry of pectin polymers transforming into submicrospheres in aqueous condition. The characteristic differences of submicrospheres were assessed by scanning electron microscopy, differential scanning calorimetry and Fouriertransform infrared spectroscopy. The average diameters of the submicrospheres ranged between 250 and 500 nm. The encapsulation efficiency of submicrospheres ranged between 80 and 96 %. The characteristic swelling behavior of lyophilized submicrospheres was influenced by the ratio of pectin polymers and folic acid used in the formulations. The submicrospheres systems exhibited controlled release of folic acid due to the pH-dependent solubility of pectin polymers in aqueous medium. The submicrospheres showed good haemocompatibility suggesting them to be promising candidates for oral delivery.

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“…Interference of abnormal metabolism in the pathogenesis of neurological and vascular diseases has been published (11). The importance of folates and other nutrients during critical stages of pregnancy is currently recognized.…”

Section: Introductionmentioning

confidence: 99%

Impact of asphyxia on red blood cell folate concentration levels in newborns

Revakova¹,

Vasilenkova²,

Ujházy³

et al. 2015

BLL

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OBJECTIVES: To determine whether red blood cell (RBC) folate concentration levels are correlated with the occurrence of neonatal asphyxia and to study the effects of gestational age, gender, and mode of delivery on RBC folate concentration levels in newborns. BACKGROUND: Asphyxia is one of the frequent causes of morbidity and mortality of newborns. Severe perinatal asphyxia can arise due to many factors. METHODS: In a prospective study, the RBC folate concentrations were determined on day 1 of life in the whole group (n = 181) of full-term (n = 121) and preterm (n = 60) newborns. Immunochemical analysis for the determination of folate in erythrocytes was performed. RESULTS: RBC folate concentration levels in asphyxiated newborns (n = 16) were signifi cantly decreased (median 974 ng/ml; p = 0.023) in comparison with healthy newborns. On the other hand, the RBC folate concentration levels were signifi cantly increased in preterm newborns (median 1,212 ng/ml; p = 0.01) in comparison with full-term newborns (median 1,098 ng/ml). Higher RBC folate concentration levels were found in newborns which had been delivered by Caesarean section (median 1,188 ng/ml; p = 0.02) compared to those born vaginally (median 1,098 ng/ml). CONCLUSION: Our results confi rmed a signifi cant decrease in RBC folate concentration in asphyxiated newborns on their fi rst day of life (Fig. 4, Ref. 36). Text in PDF www.elis.sk.

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The history of folic acid

Cited by 139 publications

References 84 publications

Structures of human folate receptors reveal biological trafficking states and diversity in folate and antifolate recognition

Structures of human folate receptors reveal biological trafficking states and diversity in folate and antifolate recognition

Evaluation of Surfactants-Assisted Folic Acid-Loaded Pectin Submicrospheres: Characterization and Hemocompatibility Assay

Impact of asphyxia on red blood cell folate concentration levels in newborns

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