Binding Characteristics of Folate to High Affinity Folate Binding Protein Purified from Porcine Serum.

Natsuhori, Masahiro; Okada, Maki; Ida, Ryo; Sasaki, Kenji; Shimoda, Minoru; Kokue, Eiichi

doi:10.1292/jvms.61.743

Cited by 7 publications

(1 citation statement)

References 21 publications

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“…Large quantities of proteins capable of binding folates, most importantly folate binding proteins (FBP), are found in clinical samples, rendering folates unavailable for analysis. Total folate measurement requires release of these bound folates via protease treatment or via gentle acidification, since both the specific (FBP) and non-specific binding capacity is negligible below pH 4 [50].…”

Section: Enzyme Treatmentmentioning

confidence: 99%

Clinical determination of folates: recent analytical strategies and challenges

et al. 2019

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Since the introduction of liquid chromatography tandem mass spectrometry in clinical laboratories, folate analysis has shifted from microbiological or protein binding assays to chromatographic methods. Now it is possible to sensitively and selectively determine several folate species in clinical samples where only a total folate content could be quantified using a microbiological or a binding assay. Although several chromatographic methods have been developed, validated and published, interlaboratory variability limits the comparability of the results. In this review we provide an overview of the latest strategies for sampling, sample treatment and analysis and how these may influence the final analytical result. Amongst the variables covered are the effect of pH, temperature, storage and the use of antioxidants and anticoagulants on analyte stability. In addition, we highlight the importance of correct assay calibration and the use of (labeled) certified reference materials in order to obtain correct and comparable results among different laboratories.

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Section: Enzyme Treatmentmentioning

confidence: 99%

Clinical determination of folates: recent analytical strategies and challenges

et al. 2019

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Folic acid inhibits 5‐methyltetrahydrofolate transport across the blood–cerebrospinal fluid barrier: Clinical biochemical data from two cases

et al. 2022

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Objective The use of folic acid (FA) has been discouraged in cerebral folate deficiency (CFD) because, theoretically, it could inhibit the transport of 5‐methyltetrahydrofolic acid (5MTHF) across the blood–cerebrospinal fluid (CSF) barrier. We present the clinical biochemical data of two cases with CFD to support this hypothesis. Methods We measured CSF and serum 5MTHF concentrations in a patient with Kearns‐Sayre syndrome (KSS) and a patient homozygous for MTHFR C677T polymorphism before and during folate supplementation therapy. To evaluate these 5MTHF concentrations, we also analyzed CSF and serum samples in pediatric patients without folate supplementation. Results Both patients had low CSF 5MTHF before treatment and high‐dose FA therapy did not normalize CSF 5MTHF. There was a dissociation between serum total folate and 5MTHF concentrations during FA therapy, which was considered to be due to the appearance of unmetabolized FA. The addition of folinic acid did not improve low CSF 5MTHF in the KSS patient and the cessation of FA resulted in the normalization of CSF 5MTHF. In the patient homozygous for MTHFR C677T, minimization of the FA dosage resulted in the normalization of CSF 5MTHF and an increased CSF‐to‐serum 5MTHF ratio. Conclusions Our data suggest that excess supplementation of FA impaired 5MTHF transport across the blood–CSF barrier. In the treatment of CFD, supplementation of folinic acid or 5MTHF (in cases of impaired 5MTHF synthesis) is preferred over the use of FA. The reference values of CSF 5MTHF concentration based on 600 pediatric cases were also provided.

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Progressive ataxia and myoclonic epilepsy in a patient with a homozygous mutation in the FOLR1 gene

Pérez‐Dueñas

Toma

Ormazábal

et al. 2010

J of Inher Metab Disea

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Several unrelated disorders can lead to 5-methyltetrahydrofolate (5MTHF) depletion in the cerobrospinal fluid (CSF), including primary genetic disorders in folate-related pathways or those causing defective transport across the blood-CSF barrier. We report a case of cerebral folate transport deficiency due to a novel homozygous mutation in the FOLR1 gene, in an effort to clarify phenotype-genotype correlation in this newly identified neurometabolic disorder. A previously healthy infant developed an ataxic syndrome in the second year of life, followed by choreic movements and progressive myoclonic epilepsy. At the age of 26 months, we analyzed CSF 5MTHF by HPLC with fluorescence detection and conducted magnetic resonance (MR) imaging and spectroscopy studies. Finally, we performed mutational screening in the coding region of the FOLR1 gene. MR showed a diffuse abnormal signal of the cerebral white matter, cerebellar atrophy and a reduced peak of choline in spectroscopy. A profound deficiency of CSF 5MTHF (2 nmol/L; NV 48-127) with reduced CSF/plasma folate ratio (0.4; NV 1.5-3.5) was highly suggestive of defective brain folate-specific transport across the blood-CSF/brain barrier. Mutation screening of FOLR1 revealed a new homozygous missense mutation (p.Cys105Arg) that is predicted to abolish a disulfide bond, probably necessary for the correct folding of the protein. Both parents were heterozygous carriers of the same variant. Mutation screening in the FOLR1 gene is advisable in children with profound 5MTHF deficiency and decreased CSF/serum folate ratio. Progressive ataxia and myoclonic epilepsy, together with impaired brain myelination, are clinical hallmarks of the disease.

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Binding Characteristics of Folate to High Affinity Folate Binding Protein Purified from Porcine Serum.

Cited by 7 publications

References 21 publications

Clinical determination of folates: recent analytical strategies and challenges

Clinical determination of folates: recent analytical strategies and challenges

Folic acid inhibits 5‐methyltetrahydrofolate transport across the blood–cerebrospinal fluid barrier: Clinical biochemical data from two cases

Progressive ataxia and myoclonic epilepsy in a patient with a homozygous mutation in the FOLR1 gene

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