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PubMed2004

Solution structure of folic acid. Molecular mechanics and NMR investigation.

The structure of folic acid in solution was investigated by nuclear magnetic resonance (NMR) and theoretical calculations. Dynamical information and geometrical constraints were obtained by carbon-13 relaxation study, homo-nuclear NOESY spectra and hetero-nuclear 1H-13C NOE experiments. This set of experimental data was used for the molecular mechanics and molecular dynamic calculations. The accuracy of the final structure was established by the R(NMR) factor, which was calculated comparing the experimental NOESY cross-peaks intensities and the corresponding values simulated by using the complete relaxation matrix analysis (CORMA) approach.

Carbon Isotopes↗
PubMed2002

Fluorescence of pterin, 6-formylpterin, 6-carboxypterin and folic acid in aqueous solution: pH effects.

Steady-state and time-resolved studies have been performed on four compounds of the pterin family (pterin, 6-carboxypterin, 6-formylpterin and folic acid) in aqueous solution, using the single photon counting technique. The fluorescence characteristics (spectra, quantum yields, lifetimes) of these compounds and their dependence on the pH have been investigated. Most pterins can exist in two acid-base forms over the pH range between 3 and 13. Emission spectra and excitation spectra were obtained for both forms of each compound studied. Fluorescence quantum yields (phi(F)) in acidic and basic media were measured. The phi(F) of folic acid (< 0.005 in both media) is very low compared to those of pterin (0.27 in basic media and 0.33 in acidic media), 6-carboxypterin (0.18 in basic media and 0.28 in acidic media) and 6-formylpterin (0.07 in basic media and 0.12 in acidic media). The variation in integrated fluorescence intensity and fluorescence lifetimes (tau(F)) was analysed as a function of pH. Dynamic quenching by OH- was observed and the corresponding bimolecular rate constants for quenching of fluorescence (k(q)) were calculated. The reported values for k(q) (M(-1) s(-1)) are 3.6 x 10(9), 1.9 x 10(9) and 1.1 x 10(10) M(-1) s(-1) for pterin, 6-carboxypterin and 6-formylpterin, respectively.

Fluorescence↗
PubMed2002

Benefits and risks of folic acid to the nervous system.

During three decades of neurological practice I have witnessed a remarkable change in attitudes to the benefits and risks of folic acid therapy in nervous system disorders. In the 1960s all that was known and taught was that folic acid was harmful to the nervous system, especially in precipitating or exacerbating the neurological complications of vitamin B12 deficiency. So deeply held was this view that the possibility of neuropsychological benefits from this vitamin was initially viewed with considerable scepticism.

Affect↗
PubMed1984

Effects of folic acid upon filopodia of Dictyostelium discoideum vegetative amoebae.

Living vegetative D, discoideum amoebae were studied to determine whether their filopodia respond to folic acid, a chemoattractant for these cells. Exponentially growing amoebae (ca. 10 micron diameter) exhibit 5-30 micron long filopodia; at stationary phase, aggregation competent amoebae have numerous multibranched filopodia up to 100 micron long. Folic acid was observed to stimulate production, elongation, and branching of filopodia with its effects progressively changing as the amoebae approach aggregation. Filopodial construction was also found to be dependent upon Mg2+ levels. The significance of these results is discussed with respect to progressive changes within the vegetative phase as well as to the mechanisms of amoeboid movement, pseudopodial activity, and chemotaxis.

Chemotaxis↗
PubMed1973

Serum folic acid activity (L. casei) in Sephadex gel chromatography.

The folic acid activity (FAA) of the protein zone in DEAE Sephadex A-50 chromatography of normal serum showed the following distribution: most (about 40%) was eluted with protein zone IV (alpha-2-macroglobulin), about 33% with protein zones II-III (transferrin), and the balance with zone V (albumin). In healthy human subjects the variations were relatively small. The repeatability of the chromatography in an individual was good.Towards the end of pregnancy the binding of FAA to protein zones II-III increased, while that to zone IV decreased. The return to normal started a few days after delivery. The binding to zones II-III was greatly increased in patients with pernicious anaemia but no neuropathy. It became normal during B(12) therapy. If the patient had neuropathy, his FAA chromatogram was close to normal. During therapy the amount of unbound FAA decreased rapidly. The use of diphenylhydantoin increased the binding of FAA to protein zone I and to zones II-III. In these patients the binding to protein zone IV was slighter than normal.

Albumins↗
PubMedDate not supplied

Clinical interpretations of the measurement of folic acid and vitamin B12 in neuromuscular disease.

56 patients were studied in an attempt to define neurologic complications associated with folic acid and vitamin B12 deficiency. 2 patients had abnormal levels of vitamin B12. 1 of these showed decreased vibRATORY SENSE IN THE LEGS. 10 of 15 patients with serum folate less than 4.0 ng per ml and 16 of 23 patients with serum folate less than 6.0 ng per ml by radioassay had neurologic abnormalities. The control group demonstrated 17/31 with neurologic abnormalities, a figure not significantly different from the deficient group. It is suggested that more patients with "pure folate deficiency" must be analyzed to eliminate the possible role of toxic effects of alcohol and other diseases of the nervous system in patients with low serum folate and neurologic problems.

Adolescent↗
PubMed1994

Effect of various amounts of folic acid added to rat food on food intake and some parameters of carbohydrate metabolism.

Male Wistar rats were given for 14 days folic acid as an addition to standard LSM food at the doses of 0.22 mg (group II), 2.2 mg (group III), 2.6 mg (group IV), 11 mg (group V) and 16.5 mg (group VI) per day/rat. In the beginning a decrease in body weight was observed and from the 7th day the weight started to increase to reach control value in all groups on the 14th day. Food intake was deteriorating with the acid concentration. The increased glucose and decreased insuline level in rat blood serum which were highly significant for groups IV and V as compared to control for the former parameter and significant for group V as compared to groups I and II for insuline indicate an effect of the excess of vitamin on endocrine function of pancreas. Increase in the muscle glicogen may result from intensified glicogenesis and gliconeogenesis processes due to folic acid.

Animal Feed↗
PubMedDate not supplied

[Stability of folic acid and vitamin B12 in TPN].

The stability of folic acid (FA) in mixtures of Total Parenteral Nutrition has been and is a controversial subject, with discussion concerning the influence of factors such as temperature, light and storage time. As regards the stability of the vitamin B12, there are few studies in scientific literature. For all those reasons, we consider it necessary to make a proper study to evaluate the influence of different factors in the stability of both vitamins. The study was made on 3 liter TPN bags of the EVA type, the composition of which was as follows: AA (85g), glucosa (225g), fat (50g), Na (86mEq), K (60 mEq), Ca (15 mEq), Cl (90 mEq), P (17 mmol) acetate (149 mEq) and 10 ml of MVI-12 which contain 400 micrograms of PA and 5 micrograms of Vitamin B 12. Consideration was also given to the stability of these two vitamins in the same diet, to which were added 10 ml of a commercial preparation of oligo-elements. Six TPN bags were prepared (without oligo-elements); two of them were kept in a fridge and protected from the light, two were kept at room temperature and protected from the light and the other two at room temperature without protection from the light. Samples were taken from all the bags immediately after their preparation and after 24, 48, 72 and 96 hours. The same process was carried with other TPN bags which did contain oligo-elements. The method for determining FA and Vitamin B12 was by radioassay.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Stability↗
PubMed1996

[An adult case of homocystinuria probably due to methylenetetrahydrofolate-reductase deficiency--treatment with folic acid and the course of coagulation-fibrinolysis parameters].

We report a rare male case of homocystinuria probably due to methylenetetrahydrofolate-reductase deficiency. The onset of his disorder was at 19 years of age, and he had no family history. He initially developed gait disturbance, and then generalized seizure in several months, which made him admitted to our hospital. Neurological examinations revealed mental dysfunction, spastic paraplegia, cerebellar ataxia, and sensory disturbance in his feet. MRI showed multiple increased intensities on T2-weighted images in the cerebral white matter. EMG revealed neurogenic changes. These symptoms and signs slowly progressed, and he then developed thrombophlebitis in his lower extremities. Thrombin-antithrombin III complex (TAT) and D-dimer remained high continuously, and plasma homocysteine level was more than ten times higher than the normal range. Plasma cystathionine level was high and methionine level was low. The serum folic acid, vitamin B12, and methylmalonic acid in the urine were normal. Megaloblastic anemia was not seen. Based on these data, he was diagnosed to have homocystinuria probably due to methylenetetrahydrofolate-reductase deficiency. Treatment with high doses of folic acid, pyridoxine and cobalamin normalized plasma cystathionine and methionine levels, and markedly decreased plasma homocysteine, although it remained about three times higher than the normal range. Thereafter, both TAT and D-dimer levels also markedly decreased. The administration of folic acid reduced elevated plasma homocysteine as well as the coagulation--fibrinolysis factors. This implies that they may serve as useful markers for effective treatment of this disease.

Adult↗
PubMed2000

[Prevalence of neural tube defects in births before and after promotion of periconceptional folic acid supplementation].

OBJECTIVE: To describe the incidence and the expected clinical picture of neural tube defects (NTD) in years when periconceptional folic acid use increased. DESIGN: Descriptive. METHOD: Data on the prevalence of NTD in the Netherlands in 1994-1998 and on the prognosis at the time of the report obtained from the Nederlands Signalerings Centrum Kindergeneeskunde (Netherlands Paediatric Spotting Centre), where all practising physicians in the Netherlands monthly report children in whom a rare disease has been diagnosed. Prevalence figures from before and after 1996 were compared, because periconceptional use of folic acid increased since late 1996. RESULTS: In 1994-1998, 414 children with NTD were reported, 164 boys, 191 girls and 59 unreported. The prevalence of NTD was 4.6 per 10,000 live births (95% confidence interval (CI): 3.7-5.6) compared with 3.8 per 10,000 live births (95% CI: 2.9-4.6) in the period 1997-1998. Of the 414 children, 257 had a meningomyelocele; the early mortality in this group amounted to 37%. Hydrocephalus was found in 84.8% of the infants, 40.9% of the infants were believed never be able to sit, stand, and walk. CONCLUSION: The prevalence of NTD was lower in the period 1997-1998 than in the period 1994-1996 although the difference was not statistically significant.

Female↗
PubMed2002

Serum iron, ferritin, folic acid, and vitamin B12 levels in recurrent aphthous stomatitis.

BACKGROUND: The exact aetiology of recurrent aphthous stomatitis (RAS) is still unknown, but different predisposing factors, including iron, vitamin B12 and folic acid deficiencies, have been proposed. MATERIAL AND METHODS: Serum iron, ferritin, folic acid and vitamin B12 levels were investigated in 35 patients with RAS and in 26 healthy controls. RESULTS: Vitamin B12 levels were found significantly lower in subjects with RAS than in controls. No significant differences were found in other parameters. CONCLUSION: We concluded that vitamin B 12 deficiency may be an aetiological factor in recurrent aphthous stomatitis.

Adolescent↗
PubMed2005

[Prevention of neural tube defects with periconceptional folic acid supplementation in Europe].

The conclusion of a report recently published by EUROCAT is that the potential for preventing neural tube defects with periconceptional folic acid supplementation is still far from being fulfilled in Europe. A number of recommendations to increase periconceptional folate status are made. In Denmark less than 20% of pregnant women follow the official recommendations on periconceptional folic acid supplementation, making the conclusions of the EUROCAT report relevant.

Denmark↗
PubMed2006

Folic acid and the treatment of depression.

Reduced plasma, serum, or red blood cell folate is commonly found in major depressive illnesses. Supplementing antidepressant medication with folic acid enhances the therapeutic effect. Although more work is required to confirm these beneficial results, it is suggested that, meanwhile, 2 mg of folic acid should be given during the acute, continuation, and maintenance treatment of depression.

Major Depressive Disorder↗
PubMed2004

Determination of folic acid in tablets by microemulsion electrokinetic chromatography.

A microemulsion electrokinetic chromatography (MEEKC) method has been developed and validated for the determination of folic acid, a water-soluble vitamin, in a commercial tablet formulation. The analysis was performed using a microemulsion containing 0.5% (w/w) ethyl acetate, 1.2% (w/w) butan-1-ol, 0.6% (w/w) sodium dodecyl sulfate, 15% (v/v) 2-propanol and 82.7% (w/w) 10 mmol L(-1) sodium tetraborate aqueous buffer at pH 9.2. Direct UV detection at 214nm led to an adequate sensitivity without interference from sample excipients. For quantitative purposes, niacin was used as internal standard. Acceptable precision (<1.2% relative standard deviation (R.S.D.)), linearity (r = 0.9992; range from 160.0 to 240.0 microg/mL), sensitivity (limit of detection (LOD) = 2.98 microg/mL; limit of quantification (LOQ) = 9.05 microg/mL) and recovery (99.8 +/- 1.8% at three concentration levels) were obtained. Based on the performance characteristics, the proposed methodology was found suitable for the determination of folic acid in tablet formulations.

Chromatography, Micellar Electrokinetic Capillary↗
PubMed1980

Metabolic responses of folic acid and related compounds to thyroxine in rats.

This study deals with the effects of thyroidectomy and feeding thyroid powder on histidine and folic acid metabolism. Normal rats maintained on a soy protein diet, low in methionine but supplemented with vitamin B-12, oxidize approx. 10% of an injected dose of [2-14C]histidine in 3 h and excrete low levels of formiminoglutamic acid. Addition of methionine increases histidine oxidation to approx. 20%. The feeding of thyroid powder or the injection of high levels of thyroxine decreases histidine oxidation and increases formiminoglutamic acid excretion. Surgical thyroidectomy at weaning increases histidine oxidation to approx. 45% and, thus, resembles the effect of methionine in promoting histidine oxidation and decreasing formiminoglutamic acid excretion. The feeding of methionine to the thyroidectomized animal further increases histidine oxidation to 65%. The distribution of folate forms in the liver was determined by column chromatography following administration of a dose of tritiated folic acid. In the normal animal, tetrahydrofolate accounts for 38% of the total folate present. The feeding of methionine increases this to 48%, which is consistent with the observed increase in histidine metabolism. Thyroidectomy increases the percentage of tetrahydrofolate to 63% and the feeding of methionine further increases it to 68%. The percentage of tetrahydrofolate relative to total folate is in proportion to the observed rate of histidine metabolism. The action of thyroidectomy in increasing histidine oxidation may be accounted for by its effect in increasing the proportion of tetrahydrofolate.

Animals↗