Biosynthesis of folic acid

Summary Biosynthesis of folic acid activity by Bacillus subtilis cell suspensions was studied with respect to substrates utilized as precursors. Among purine bases, adenine was utilized the best and not guanine although guanosine or guanylic acid were utilized efficiently. Among 3-C precursors, glyceraldehyde gave maximum synthesis of folate activity. The cells appeared to utilize p-aminobenzoate preferentially to p-aminobenzoyl-glutamate. Pteroic acid appears to be an intermediate in the synthesis of folate derivatives in this system. Ascorbic acid stimulates the synthesis to a great extent.     

Bacterially synthesized folate and supplemental folic acid are absorbed across the large intestine of piglets

A large pool of folate exists in the large intestine of humans. Preliminary evidence, primarily in vitro, suggests that this folate may be bioavailable. The purpose of this study was to test the hypothesis that supplemental folic acid and bacterially synthesized folate are absorbed across the large intestine of piglets. The pig was used as an animal model because it resembles the human in terms of folate absorption, at least in the small intestine. A tracer of [3H]-folic acid or [3H]-para-aminobenzoic acid ([3H]-PABA), a precursor of bacterially synthesized folate, was injected into the cecum of 11-day-old piglets. Feces and urine were collected for 3 days. Thereafter, piglets were killed, and livers and kidneys harvested. [3H]-Folate was isolated from biological samples by affinity chromatography using immobilized milk folate binding proteins and counted using a scintillation counter. In piglets injected with [3H]-folic acid, the feces, liver, urine and kidneys accounted for 82.1%, 12.3%, 3.9% and 1.7% of recovered [3H]-folate, respectively. In piglets injected with [3H]-PABA, the amount of recovered bacterially synthesized folate in the feces, liver and urine was 85.1%, 0.4% and 14.6%, respectively. Twenty-three percent and 13% of tritium were recovered in samples examined (liver, kidney, fecal and urine) from piglets injected with [3H]-folic acid and [3H]-PABA, respectively. Using our estimates of [3H]-folic acid absorption and the total and percent monoglutamyl folate content of piglet feces, we predict that at least 18% of the dietary folate requirement for the piglet could be met by folate absorption across the large intestine.     

Uracil misincorporation into DNA of leukocytes of young women with positive folate balance depends on plasma vitamin B12 concentrations and methylenetetrahydrofolate reductase polymorphisms. A pilot study

Changes in the folate and vitamin B12 status in the body influence the extent of uracil misincorporation (UrMis) into DNA, which is one of the biomarkers of genomic stability and, thus, portends a risk of cancer. In our study, the level of UrMis into DNA was evaluated by the comet assay (using the specific DNA repair enzyme, uracil DNA glycosylase) in leukocytes from blood donated by healthy young women with positive folate balance achieved by 4 weeks of folic acid supplementation (400 microg/day). The nutritional status was evaluated on the basis of nine food diaries recorded by the subjects during two winter months. The data were computerized, and the intake of nutrients and micronutrients was estimated using the DIETA 2 program (Food and Nutrition Institute, Warsaw, Poland) linked to recently updated Polish food tables. The plasma folate and vitamin B12 concentration, as well as methylenetetrahydrofolate reductase (MTHFR) polymorphisms, were evaluated to determine their influence on the level of UrMis into DNA. The mean value of B12 intake for all subjects reached 100% of the Polish recommended dietary allowances (RDA), whereas the mean value of folate intake, before folate supplementation, was 50%, suggesting moderate deficiency. Folic acid supplementation brought the folate intake way above the RDA, and plasma folate concentration in each individual was above the deficient range (mean value 14.67 ng/ml). The UrMis did not correlate with the plasma folate concentration, but the level of UrMis was significantly lower in subjects with plasma vitamin B12 concentration above 400 pg/ml (P=.02) only after folic acid supplementation. The concentration of folate in plasma correlated (P相似文献   

Theoretical studies on the activation of the pterin cofactor in the catalytic mechanism of dihydrofolate reductase

Two mechanisms for facilitating hydride ion transfer from NADPH involving preprotonation of the pteridine rings of the dihydrofolate reductase substrates folate and dihydrofolate have been investigated by ab initio quantum mechanical methods. Protonation energies and effective solution pKas have been calculated for four protonated forms, three of which are nonpreferred in aqueous solution and therefore not directly accessible to experimental study. The pattern and degree of redistribution of the positive charge over the component rings of the N-heterobicyclic pi-system in these protonated forms have been analyzed in terms of changes in the electron populations of the ring atoms and total ring charges. The effects of such changes in promoting hydride ion transfer to C7 in folate and C6 in dihydrofolate have been evaluated by considering the extent of development of partial carbonium ion character at these carbon atoms and also the degree of electron deficiency in the pyrazine ring as a whole. The results illustrate that perturbations due, for instance, to protonation may be propagated by pi-electron coupling effects over medium-range distances of 4-6 A across the pteridine ring. The two mechanisms have been assessed in terms of the calculated absolute and relative pKas of the protonated species taking into account experimental information regarding possible stabilization of these forms in the enzyme active site and also the effectiveness of the various protonations in assisting the hydride ion transfer step. Judged against these criteria, the theoretical results favor the generally proposed mechanism involving preprotonation of N8 in folate and N5 in dihydrofolate. However, some support was also found for the alternative novel mechanism involving O4-protonation of both folate and dihydrofolate.     

Folate transport in Lactobacillus salivarius. Characterization of the transport mechanism and purification and properties of the binding component

Lactobacillus salivarius cells contain an inducible transport system for folate. Influx via this system is time- and temperature-dependent, requires glucose and glutamine for optimum activity, and is half-maximal at folate concentrations in the nanomolar range. The folate internalized after 30 min at 30 degrees C is not released from the cells by excess extracellular folate and is recovered in cell extracts primarily in metabolized forms. A membrane-associated folate-binding protein is also present in cells that have been induced to transport folate. This binding protein constitutes 1% of total cellular protein, exhibits a high affinity for folate (KD = 0.40 nM), and requires divalent cations for optimum binding activity. Folate binds rapidly to this protein, while the exchange of bound substrate with folate added subsequently is relatively slow and dependent on the metabolic state of the cell. The transport rate per binding site is 0.05/min at 30 degrees C. A comparison of substrate specificity showed that folate binding and transport are both inhibited to the same extent by several different folate compounds, and a parallel irreversible inhibition of both processes is observed by prior treatment of the cells with a carbodiimide-activated derivative of folic acid. Binding protein labeled covalently with [3H]folate and solubilized with Triton X-100 was purified by a fractionation procedure involving absorption and elution from microgranular silica and molecular sieve chromatography. The isolated protein appeared homogeneous by gel electrophoresis and had an apparent molecular weight of 21,000. Monoclonal antibodies to the folate transport protein of Lactobacillus casei showed a high degree of cross-reactivity to the isolated binding protein from L. salivarius, indicating that these proteins share common epitopes. These results suggest that folate uptake by L. salivarius proceeds via an abundant membrane-associated binding protein which facilitates the movement of folate across the membrane as an electroneutral complex with cations. The substrate then slowly dissociates from internalized binding sites and is metabolized sequentially to coenzyme forms and then to membrane-impermeable folylpolyglutamates.     

In situ autoradiographic detection of folylpolyglutamate synthetase activity

The enzyme folylpolyglutamate synthetase (FPGS) catalyzes the conversion of folate (pteroylmonoglutamate) to the polyglutamate forms (pteroylpolyglutamates) that are required for folate retention by mammalian cells. A rapid in situ autoradiographic assay for FPGS was developed which is based on the folate cofactor requirement of thymidylate synthase. Chinese hamster AUX B1 mutant cells lack FPGS activity and are unable to accumulate folate. As a result, the conversion of [6-3H]deoxyuridine to thymidine via the thymidylate synthase reaction is impaired in AUX B1 cells and no detectable label is incorporated into DNA. In contrast, FPGS in wild-type Chinese hamster CHO cells causes folate retention and enables the incorporation of [6-3H]deoxyuridine into DNA. Incorporation may be detected by autoradiography of monolayer cultures or of colonies replica plated onto polyester discs. Introduction of Escherichia coli FPGS into AUX B1 cells restores the activity of the thymidylate synthase pathway and demonstrates that the E. coli FPGS enzyme can provide pteroylpolyglutamates which function in mammalian cells.     

The utilization of formate by human erythrocytes

The incorporation of radioactive formate into an acid-stable non-volatile form by human erythrocytes is dependent upon the addition of 5-amino-4-imidazolecarboxamide riboside. The formate-incorporating activity of human erythrocytes varies widely among normal individuals and the values obtained are characteristic of the erythrocytes obtained from these individuals. The variation is unrelated to the total folate levels of the erythrocytes as measured by the growth response of Lactobacillus casei but is roughly correlated with the quantity of folate forms in the erythrocytes which support the growth of Steptococcus faecalis. The activities of several enzymes involved in the metabolism of the folate coenzymes has also been measured in extracts of erythrocytes. Extracts from all the individuals contained 10-formyltetrahydrofolate synthase, 5-amino-4-imidazolecarboxamide ribotide transformylase, and 5,10-methylenetetrahydrofolate dehydrogenase. None of the extracts contained detectable quantities of either 5,10-methylenetetrahydrofolate reductase or 5-methyltetrahydrofolate-homocysteine methyltransferase. These data support the conclusion that 5-methyltetrahydrofolate is not in metabolic equilibrium with the other forms of folate in the erythrocyte and the uptake of formate by intact erythrocytes is a function of those forms of the folate coenzymes which can be converted to tetrahydrofolate.     

Differential binding of folates by rat renal cortex brush border and basolateral membrane preparations

The binding of radioactive 5-methyltetrahydrofolate and folic acid was found to be greater in brush border than in basolateral membrane preparations of rat renal cortex. This appeared to be due to an increased amount of a specific folate binding protein in the brush border membrane preparations as compared to those of the basolateral membrane. The binding was saturable and inhibited by nonradioactive folic acid and, therefore, a specific, rather than nonspecific process. The Km's for folic acid binding in brush border and basolateral membrane preparations were similar and involved a single high-affinity binding site. In contrast, methotrexate was found to bind equally well to both brush border and basolateral membrane preparations. Moreover, folic acid binding was not inhibited by an equimolar amount of methotrexate. A folate binding protein could be extracted from either membrane preparation with 1% Triton X-100 and, to a lesser extent, with 0.6 M NaCl. These different extraction procedures resulted in different apparent molecular weights for folate binding protein (greater than 160,000 for Triton X-100-extracted samples and 40,000 for NaCl-extracted samples). The membrane preparation pellets remaining after NaCl extraction were able to rebind tritiated folic acid and also the 40,000-Da folate binding protein. On the other hand, membrane preparations extracted with Triton X-100 lost the ability to bind folic acid or the 40,000-Da folate binding protein. These differences in molecular weight and rebinding capacity may be explained by the existence of a receptor for folate binding protein which was extracted by Triton X-100, but not by NaCl. The greater concentration of folate binding protein in the renal tubule cell brush border membrane preparations as compared to those from basolateral membranes ascribes, for the first time, a functional role for folate binding protein in the renal reabsorption of folates which is required to prevent loss of folate in the urine and perhaps in the membrane transport of folates in general.     

Role of the membrane-associated folate binding protein (folate receptor) in methotrexate transport by human KB cells

The uptake of methotrexate by KB cells was observed to be dependent on time, temperature, and concentration of extracellular methotrexate. The Kd for methotrexate surface binding to KB cells was approximately 200 nM. Following exposure of KB cells to trace quantities of [3H]methotrexate for periods ranging from 6 min to 24 h, the cellular methotrexate was progressively formed into methotrexate polyglutamates and was bound to dihydrofolate reductase as well as to a particulate folate binding protein. To further study the mechanism of methotrexate uptake in KB cells, the N-hydroxysuccinimide ester of methotrexate was used to covalently label the surface of KB cells and to inhibit transport of methotrexate. The N-hydroxysuccinimide ester of methotrexate was bound to a species of protein with an apparent molecular weight of 160,000 in 1% (v/v) Triton X-100 that bound folic acid and was specifically precipitated by antiserum raised against the previously purified high-affinity folate binding protein (the folate receptor) from human KB cells. In addition, trypsin was utilized to remove surface-accessible covalently bound methotrexate. The amount of covalently bound methotrexate that could be released by trypsin initially decreased on incubation at 37 degrees C, suggesting that the methotrexate and binding protein were internalized. However, with time, trypsin could again release the covalently bound methotrexate, suggesting that the binding protein cycles from the external cell surface to the inside of the cell and out again.     

Culture cycle dependence of folate interconversion and related enzymes in Euglena gracilis

Folates are involved in one-carbon metabolism in which one-carbon groups of increasing reduction state (formyl, methylene and methyl) are cyclically accepted and donated by the coenzyme form of folic acid, tetrahydrofolic acid. The latter originates by reduction of dihydrofolic acid, the coenzymatically inactive form. Euglena culture cycle dependence of folate distribution in oxidized, formyl and methyl forms and of enzyme activities for folate interconversion were studied. Distribution levels of all the components examined varied widely during the culture, and many of these changes occurred in the logarithmic phase of growth. In the phase of folate synthesis, there was an appreciable delay in the conversion of oxidized to reduced forms and of formyl to methyl forms. This delay appeared to be correlated with the level of corresponding enzymes. The methyl folate peak coincided with the highest level of total cell folates, at which point a severe repression of folate synthesis began. During the last phase of exponential growth, when cell folate content was reduced to one-fifth and folates had shorter glutamate chains, the level of coenzymatically inactive and inhibitory oxidized forms increased again. The reduced efficiency of the system and the change in growth rate are discussed. The activity patterns of dihydrofolate reductase and methylene tetrahydrofolate reductase were markedly different. The peak in methylene tetrahydrofolate reductase activity coincided with the absence of oxidized folates. A regulation of folate synthesis by the level of methyl folates and of methylene tetrahydrofolate reductase synthesis by the level of oxidized forms is proposed.     

Kinetic evidence for two interconvertible forms of the folate transport protein from Lactobacillus casei.

Lactobacillus casei cells contain a folate transport protein which exhibits a high affinity for folate. The dissociation constant (KD) for folate derived from binding parameters at the steady state (at 0 degree C) is 0.4 nM at pH 7.5 and 0.1 nM at pH 6.0. In the present study, folate binding to this protein at pH 7.5 (and 0 degree C) was shown to follow second-order kinetics and to proceed with an association constant (k+1) of 4.9 X 10(7) liter/mol per min. K+1 was not affected by preincubation conditions which alter the energetic state of the cell. Measurements on the extent of binding showed further that (at 0 degree C) essentially all unoccupied folate-binding sites reside at or are readily accessible to the outer surface of the membrane. In contrast, after saturating the binding site with [3H]folate, the first-order rate constant (k-1) for dissociation of the bound substrate (at 0 degree C) was found to vary substantially with the conditions employed. k-1 was 0.028/min in freshly harvested cells, but it increased by 2.8-fold in cells preincubated at 23 degrees C for 60 min and by 5.4-fold in isolated membranes. In addition, the faster rate observed in preincubated cells (k-1 = 0.077/min) returned to a slower rate after brief exposure of the cells to pH 6.0 (k-1 = 0.041/min), glucose (k-1 = 0.050/min), or both (k-1 = 0.012/min). k-1 was twofold lower at pH 6.0 than at pH 7.5 and was less dependent on the preincubation conditions, although it also increased substantially (5.5-fold) when the cells were converted to plasma membranes. The proposed explanation for these results is that folate transport protein of L. casei exists in two forms which can be distinguished by the accessibility of the binding site to the external medium and whose amounts are dependent upon the presence of bound folate, the pH, and the energetic state of the cell. It is suggested that these forms are transport proteins with binding sites oriented towards the inner and outer surfaces of the membrane.     

Quantitative aspects of the intestinal absorption and metabolism of cholesterol and beta-sitosterol in the rat

The quantitative aspects of intestinal absorption and metabolism of cholesterol and -sitosterol have been studied in the rat after a single feeding of radioactive sterols. When increasing amounts of cholesterol were fed in a constant amount of triolein, the percentage absorbed decreased only gradually and the total amounts absorbed increased to a maximum. Solubility in the fat component fed is one limiting factor in the absorption of cholesterol. At the lowest dose fed, only about 50% of dietary cholesterol was absorbed even though increasing the amount fed led to a 10- to 15-fold increase in total absorption. Sitosterol, when fed in triolein, was absorbed in amounts only one-tenth of the corresponding dose of cholesterol. Intestinal transit studies indicate that the distinction between sitosterol and cholesterol, when fed together, took place during the process of uptake into the intestinal mucosa. Once taken up by the intestinal mucosal cells, cholesterol and sitosterol did not differ in their subsequent rate of transit out of the mucosal cell. Feeding sitosterol with cholesterol seems to have the same effect on cholesterol absorption as feeding the same additional dose of cholesterol, the difference being that sitosterol is taken up by the intestinal wall in amounts only one-tenth to one-fifth of that of cholesterol. The rapid and complete absorption of the triglyceride fat and the subsequent transit of the intestinal content to the large intestine are most probably important factors in the determination of the extent of absorption of nonglyceride fat. The mechanism behind the difference in extent of absorption of the closely related sterols is not explained.     

High molecular weight complexes of folic acid in mammalian tissues

Twenty-four hours after injection of tritiated folic acid into normal rats, a large amount of labeled folates were found to be associated with the high molecular weight fraction of liver, kidney and intestine. The bound folate was associated with three fractions in the liver cell supernatant having approximate molecular weights of ? 350,000, 150,000 and 25,000 daltons, respectively. A fourth fraction which had an approximate molecular weight of 90,000 daltons was isolated from the liver nuclear fractions. The bound folates associated with these fractions were almost exclusively polyglutamate forms.     

Significant role of the nitrogen recycling system through the ceca occurs in protein-depleted chickens

This study focuses on the role of the ceca in nitrogen nutrition in chickens (Gallus domesticus). Urea is a very good nitrogen tracer for these studies. Little urea is synthesized by chickens due to the absence of carbamyl phosphate synthetase, an essential enzyme initiating the urea cycle. Urea is utilized by chickens when crystalline amino acid diets low in nonessential nitrogen or diets containing low concentrations of intact protein are fed, and most ureolytic activity is found in the ceca. Dietary urea was absorbed intact from the upper intestine of the chicken. The absorbed urea was excreted into ureteral urine that refluxed from the cloaca into the colon and ceca where urea was degraded to ammonia. Presumably the ammonia was incorporated into amino acids by cecal microorganisms and some urea, amino acids and proteins were absorbed from the ceca. These were utilized by the chickens. A beneficial role of ceca in the nitrogen metabolism in the chicken is, therefore, conservation of urinary nitrogen in protein-depleted chickens.     

G80A reduced folate carrier SNP modulates cellular uptake of folate and affords protection against thrombosis via a non homocysteine related mechanism

Dietary folate is absorbed in the jejunum by the 'Reduced Folate Carrier' binding protein. This protein also sequesters extracellular folate for use by many cells in the body. As several biosynthetic pathways require folate for critical life processes, any change in the properties of this protein could lower folate bioavailability, cellular levels of the vitamin, and thus influence health. Since folate lowers thrombogenic homocysteine, we examined the prevalence of a common genetic polymorphism encoding the Reduced Folate Carrier (G80A RFC) to see if it acts as a risk factor for thrombotic vascular disease via an effect on homocysteine disposition in a cohort of 156 patients. The odds ratio indicates a significant protective effect of the mutant A allele against thrombosis: OR = 0.56(95% CI; 0.34-0.92). chi2; p = 0.022 (Yates corrected chi2; p = 0.031). The polymorphism had no impact on homocysteine, but did increase the level of extracellular to intracellular folate as might be predicted by the biological role of the expressed protein. This, and not homocysteine level, may be what affords protection against thrombosis.     

Oxidative Assimilation of Glucose by Scenedesmus quadricauda

The utilization of glucose by Scenedesmus quadricauda has beenstudied by manometric methods. With small amounts the oxidationonly goes to about 16 per cent. of completion, the remainderof the glucose being built up into an acid-hydrolysable polysaccharidewhich is not starch, and which is built up from a hexose otherthan fructose. The extent of the oxidation is not affected by sodium azideor 2:4-dinitro-phenol, but can be varied by altering the pHof the suspension medium; more oxygen is absorbed per unit weightof glucose at pH 8 than at pH 5. It is suggested that there is no fixed relation between thetwo processes of oxidation and synthesis, as has previouslybeen suggested, but that the glucose, after phosphorylation,saturates the oxidation system, and the excess hexose-phosphateis built up into a polysaccharide. Mannose is also utilized in the same way, but at a slower rate,and less oxygen is used up compared with glucose. Galactosegives only a slight stimulation of the respiratory rate, andfructose, sucrose, and lactose are not absorbed.     

13C-enrichment at carbons 8 and 2 of uric acid after 13C-labeled folate dose in man

To evaluate folate-dependent carbon incorporation into the purine ring, we measured (13)C-enrichment independently at C(2) and C(8) of urinary uric acid (the final catabolite of purines) in a healthy male after an independent oral dose of [6RS]-5-[(13)C]-formyltetrahydrofolate ([6RS]-5-H(13)CO-H(4)folate) or 10-H(13)CO-7,8-dihydrofolate (10-H(13)CO-H(2)folate). The C(2) position was (13)C-enriched more than C(8) after [6RS]-5-H(13)CO-H(4)folate, and C(2) was exclusively enriched after 10-H(13)CO-H(2)folate. The enrichment of C(2) was greater from [6RS]-5-H(13)CO-H(4)folate than 10-H(13)CO-H(2)folate using equimolar bioactive doses. Our data suggest that formyl C of [6RS]-10-H(13)CO-H(4)folate was not equally utilized by glycinamide ribotide transformylase (enriches C(8)) and aminoimidazolecarboxamide ribotide (AICAR) transformylase (enriches C(2)), and the formyl C of 10-H(13)CO-H(2)folate was exclusively used by AICAR transformylase. 10-HCO-H(2)folate may function in vivo as the predominant substrate for AICAR transformylase in humans.     

Compensation for PSII photoinactivation by regulated non-photochemical dissipation influences the impact of photoinactivation on electron transport and CO2 assimilation

The extent to which PSII photoinactivation affects electron transport (PhiPSII) and CO2 assimilation remains controversial, in part because it frequently occurs alongside inactivation of other components of photosynthesis, such as PSI. By manipulating conditions (darkness versus low light) after a high light/low temperature treatment, we examined the influence of different levels of PSII inactivation at the same level of PSI inactivation on PhiPSII and CO2 assimilation for Arabidopsis. Furthermore, we compared PhiPSII at high light and optimum temperature for wild-type Arabidopsis and a mutant (npq4-1) with impaired capacities for energy dissipation. Levels of PSII inactivation typical of natural conditions (< 50%) were not associated with decreases in PhiPSII and CO2 assimilation at photon flux densities (PFDs) above 150 micromol m(-2) s(-1). At higher PFDs, the light energy being absorbed was in excess of the energy that could be utilized by downstream processes. Arabidopsis plants downregulate PSII activity to dissipate such excess in accordance with the level of PSII photoinactivation that also serves to dissipate absorbed energy. Therefore, the overall levels of non-photochemical dissipation and the efficiency of photochemistry were not affected by PSII inactivation at high PFD. Under low PFD conditions, such compensation is not necessary, because the amount of light energy absorbed is not in excess of that needed for photochemistry, and inactive PSII complexes are dissipating energy. We conclude that moderate photoinactivation of PSII complexes will only affect plant performance when periods of high PFD are followed by periods of low PFD.     

The folate cofactor of Escherichia coli DNA photolyase acts catalytically

Escherichia coli DNA photolyase catalyzes the light-driven (300-500 nm) repair of pyrimidine dimers formed between adjacent pyrimidine bases in DNA exposed to UV light (200-300 nm). The light-driven repair process is facilitated by two enzyme-bound cofactors, FADH2 and 5,10-methenyltetrahydrofolate. The function of the folate has been characterized in greater detail in this series of experiments. Investigations of the relative binding affinities of photolyase for the monoglutamate and polyglutamate forms of 5,10-methenyltetrahydrofolate show that the enzyme has a greater affinity for the naturally occurring polyglutamate forms of the folate and that the exogenously added monoglutamate derivative is less tightly associated with the protein. Multiple turnover experiments reveal that the folate remains bound to photolyase even after 10 turnovers of the enzyme. Examination of the rates of repair by photolyase containing stoichiometric folate in the presence or absence of free folate under multiple turnover conditions and at micromolar concentrations of enzyme also demonstrates that the folate acts catalytically. The stimulation of turnover by exogenous folate seen at low concentrations of photolyase is shown to be due to the lower affinity of photolyase for the monoglutamate derivative used in reconstitution procedures. These results demonstrate that the folate of E. coli DNA photolyase is a bona fide cofactor and does not decompose or dissociate during multiple turnovers of the enzyme.     

Utilization of yeast polyglutamate folates in man.

Ingestion by healthy humans of small amounts of polyglutamate folates from yeast, equivalent to 300 mug of monoglutamate folate and containing 30 mug of "free folate," resulted in an appreciable elevation of the serum folate corresponding to 300 mug of synthetic pteroylmonoglutamate (PGA). Ingestion of higher amounts of polyglutamate folate did not result in higher serum folate elevations than did 300 mug. It is concluded that small amounts of polyglutamate folate from yeast are fully utilized, presumably by deconjugation in the gut prior to absorption. The relative ineffectiveness of larger doses of polyglutamate folates from yeast may be due to limiting conjugase activity in the gut, unfavorable conditions for its activity (such as unsuitable pH) or to an inhibitor of the enzyme present in impure preparations.