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PubMed1988

Inhibition of cell proliferation with antibody-targeted liposomes containing methotrexate-gamma-dimyristoylphosphatidylethanolamine.

We have prepared liposomes containing methotrexate-gamma-dimyristoylphosphatidylethanolamine (MTX-DMPE liposomes), to which protein A was covalently coupled, permitting specific association of these liposomes in vitro with murine cells preincubated with relevant protein A-binding monoclonal antibodies. In the absence of antibody the presence of externally-oriented methotrexate (MTX) in MTX-DMPE liposomes did not result in greater binding to cells than liposomes made without MTX-gamma-DMPE. Derivation of methotrexate with phospholipid permits enhanced drug-liposome association. These liposomes are more resistant than conventional liposomes to repeated cycles of freezing and thawing. MTX-DMPE liposomes are comparable to antibody-targeted liposomes made with encapsulated water-soluble methotrexate both with respect to specific binding to target cells and drug effect. The inhibitory effects of MTX-liposomes, as well as free MTX, were reversible by either thiamin pyrophosphate (Tpp) or N5-formyltetrahydrofolate (F-THF), while the effects of MTX-DMPE liposomes were reversed only by N5-formyltetrahydrofolate. This suggests that the toxicity of non-targeted MTX-liposomes may be due to leakage of the encapsulated MTX. The absence of an effect of thiamin pyrophosphate on non-targeted MTX-DMPE liposomes indicates that they do not enter into the cell via the normal folate transport system.

Ammonium Chloride↗

PubMed1980

Initiation of protein synthesis in isolated mitochondria and chloroplasts.

N5-Formyltetrahydrofolate, a competitive inhibitor of the formylation of the initiator Met-tRNAfMet in an in vitro assay, is a powerful inhibitor of amino acid incorporation in isolated Saccharomyces cerevisiae mitochondria and in Euglena gracilis chloroplasts. Thus, a large part of the incorporation is dependent upon new initiation acts. On the contrary, the rate of incorporation can be largely increased by addition of the specific formyl group donor, N10-formyltetrahydrofolate. Experiments are also reported strongly suggesting that the formylation of Met-tRNAfMet is an absolute requirement in order to initiate protein synthesis in chloroplasts, as has been shown in mitochondria.

Chloroplasts↗

PubMed1995

18Oxygen incorporation into inorganic phosphate in the reaction catalyzed by N5,10-methenyltetrahydrofolate synthetase.

The mechanism of the N5,10-methenyltetrahydrofolate synthetase reaction was probed by determining the source of the oxygen atom introduced between the beta- and gamma-phosphates as ATP is converted to ADP and Pi. The reaction was performed using a mixture of [18O]- and [16O]N5-formyltetrahydrofolate in the presence of [16O]H2O and using [16O]N5-formyltetrahydrofolate in the presence of a 1:1 mixture of [18O]H2O and [16O]H2O. 31P NMR spectroscopy was used to examine the products. It was found that 18O from the formyl group was incorporated into Pi, and that 18O was not incorporated from the solvent. The results are consistent with a mechanism involving phosphorylation of the formyl group at the N5-position, followed by displacement of the phosphate by the 10-nitrogen.

Adenosine Diphosphate↗

PubMed1987

Platinum-folate compounds: synthesis, properties and biological activity.

Cis-diamminediaquaplatinum(II)-ion, the biologically active form of the anticancer agent Cisplatin, reacted readily with tetrahydrofolate at pH 7 and 37 degrees C to produce a stable complex. The reaction was monitored spectrophotometrically by the change in absorbance maximum from 298 nm (tetrahydrofolate) to 275 nm (complex); occurrence of isobestic points at 282 and 327 nm indicated that a single product was formed. Purity of platinum-tetrahydrofolate, after isolation in ca. 70% yield, was established by TLC and HPLC. Elemental analysis, absorbance spectra at various pH values and nmr spectra provided evidence that the diammine platinum moiety was bridged across the N-5 and N-10 positions of tetrahydrofolate. Complexation also occurred with 5-methyltetrahydrofolate, 5-formyltetrahydrofolate, Methotrexate and aminopterin, but not with folate or 7,8-dihydrofolate. Biological implications of these observations have been investigated. Intracellular folates in L1210 cells have been identified and quantitated via reverse phase HPLC (C18 column; tetrabutylammonium phosphate as the pairing ion) and changes in the levels of these compounds, after exposure of cells to Cisplatin, have been measured. Platinum derivatives of tetrahydrofolate or other reduced folates were not found, but there was a decrease in the level of 5,10-methenyltetrahydrofolate, accompanied by an increase in 5-formyl and 10-formyltetrahydrofolate (and perhaps tetrahydrofolate). The chemical interaction of the diaqua form of Cisplatin with Methotrexate resulted in decreased uptake of the latter by L1210 cells. The platinum complex of tetrahydrofolate was a reasonably good inhibitor (Ki = 4 microM) of L1210 dihydrofolate reductase and of the folate transport system (50% inhibition at ca. 200 microM) of L1210 cells.

Animals↗

PubMed1987

Human liver methenyltetrahydrofolate synthetase: improved purification and increased affinity for folate polyglutamate substrates.

Methenyltetrahydrofolate synthetase (5-formyltetrahydrofolate cyclodehydrase (cyclo-ligase) (ADP-forming) EC 6.3.3.2) catalyzes the ATP- and Mg2+-dependent transformation of 5-formyltetrahydrofolate (leucovorin) to 5,10-methenyltetrahydrofolate. The enzyme has been purified 49,000-fold from human liver by a two-column procedure with Blue Sepharose followed by folinate-Sepharose chromatography. It appears as a single band both on SDS-polyacrylamide gel electrophoresis (Mr 27,000) and on isoelectric focusing (pI = 7.0) and is monomeric, with a molecular weight of 27,000 on gel filtration. Initial-velocity studies suggest that the enzyme catalyzes a sequential mechanism and at 30 degrees C and pH 6.0 the turnover number is 1000 min-1. The enzyme has a higher affinity for its pentaglutamate substrate (Km = 0.6 microM) than for the monoglutamate (Km = 2 microM). The antifolate methotrexate has no inhibitory effect at concentrations up to 350 microM, while methotrexate pentaglutamate is a competitive inhibitor with a Ki = 15 microM. Similarly, dihydrofolate monoglutamate is a weak inhibitor with a Ki = 50 microM, while the pentaglutamate is a potent competitive inhibitor with a Ki of 3.8 microM. Thus, dihydrofolate and methotrexate pentaglutamates could regulate enzyme activity and help explain why leucovorin fails to rescue cells from high concentrations of methotrexate.

Adenosine Triphosphate↗

PubMed2006

Application of liquid chromatography-electrospray ionisation mass spectrometry for determination of dietary folates: effects of buffer nature and mobile phase composition on sensitivity and selectivity.

A sensitive and reliable liquid chromatography-mass spectrometry (LC-MS) method to determine dietary folates was developed and validated. Folates were detected and quantified using positive electrospray ionisation (ESI) with selective ion monitoring of protonated ions [M+H]+. The effects of buffer nature and mobile phase composition on separation, peak shape and intensity of MS signal were investigated. The acidic-basic properties of folates were successfully used to predict possible ionisation patterns, but they were not sufficient to predict the intensity of MS signal and the proportion of different ionisation products, which indicated that other parameters, such as gas phase acidity/basicity of analytes and ion evaporation mechanisms might be important. The use of aqueous acetic acid as volatile buffer was found to be preferable compared to formic acid due to considerable gain in intensity of MS signal for all folate forms studied. Limits of quantifications were 0.3 ng/mL for 5-methyltetrahydrofolate and 0.6 ng/mL for tetrahydrofolate, 10-formylfolic acid, 5-formyltetrahydrofolate and folic acid when using 20 microL injection. For 10-formylfolic acid, 5-formyltetrahydrofolate and folic acid the MS detection was found to be superior over commonly used fluorescence and UV detection in terms of selectivity and sensitivity. The method was successfully applied to analysis of folates in baker's yeast.

Animals↗

PubMed2004

Cloning, expression, and purification of 5,10-methenyltetrahydrofolate synthetase from Mus musculus.

Folate metabolism is necessary for the biosyntheses of purine nucleotides and thymidylate and for the synthesis of S-adenosylmethionine, a cofactor required for cellular methylation reactions and a precursor of spermidine and spermine syntheses. Disruption of folate metabolism is associated with several pathologies and developmental anomalies including cancer and neural tube defects. The enzyme 5,10-methenyltetrahydrofolate synthetase (MTHFS, EC 6.3.3.2) catalyzes the ATP-dependent conversion of 5-formyltetrahydrofolate to 5,10-methenyltetrahydrofolate, and has been shown to affect intracellular folate concentrations by accelerating folate degradation. Mammalian MTHFS proteins described to date are not stable and no recombinant mammalian MTHFS protein has been successfully expressed in Escherichia coli. The three-dimensional structure of MTHFS has not been solved. The cDNA coding for Mus musculus MTHFS was isolated and expressed in E. coli with a hexa-histidine tag. Milligram quantities of recombinant mouse MTHFS were purified using metal affinity chromatography and the protein was stabilized with Tween 20. Mouse MTHFS has a molecular mass of 23kDa and is 84% identical in amino acid sequence to the human enzyme. Activity assays confirmed the functionality of the recombinant protein, with Km =5 microM for (6S)-5-formyltetrahydrofolate and Km=769 microM for Mg-ATP. This is the first example of a mammalian form of MTHFS expressed in E. coli that yielded sufficient quantities of stable purified protein to allow for detailed characterization of its three-dimensional structure and kinetic properties.

Amino Acid Sequence↗

PubMed2003

Residues 45 and 404 in the murine reduced folate carrier may interact to alter carrier binding and mobility.

The reduced folate carrier (RFC), a facilitative transporter, plays a major role in the delivery of reduced folates and antifolates into cells. Previous studies indicated that mutations of E45K in the first transmembrane domain (TMD), and K404L in the 11th TMD, produce selective and opposite alterations in binding of natural folate substrates to murine RFC. The former mutation is frequently associated with antifolate resistance. The current study was designed to determine whether there might be an interaction between these sites by comparing the transport properties of RFC-null cell lines stably transfected with K404E, E45K, or E45K/K404E carriers. These studies demonstrated that: (1) All mutant carriers were inserted into the plasma membrane. (2) In the K404E mutant, the influx K(t)'s for 5-formyltetrahydrofolate and 5-methyltetrahydrofolate were markedly increased, and to a much smaller extent folic acid, as compared to L1210 cells. However, with introduction of a second E45K mutation the influx K(t) for these folates reverted to those of the E45K cells which retained wild-type binding for 5-methyltetrahydrofolate and enhanced binding of 5-formyltetrahydrofolate and folic acid. (3) The influx V(max) of the E45K mutant was markedly reduced. Introduction of the second K404E mutation doubled this parameter and the ratio of V(max) to K(t) for 5-formytetrahydrofolate was restored to approximately 50% that of the wild-type carrier consistent with a substantial increase in function. (4) Chloride inhibits wild-type RFC but the E45K mutant requires chloride for activity. The K404E mutant is also suppressed by chloride but introduction of the K404E mutation decreased the chloride-dependence of E45K. The results suggest that there is an interaction between the E45 and K404 residues in the first and 11th TMDs, respectively, but that the E45 residue appears to be the more dominant determinant of binding and anion sensitivity.

Amino Acid Substitution↗

PubMed2002

Role of the C-terminus and the long cytoplasmic loop in reduced folate carrier expression and function.

The reduced folate carrier (RFC1), a member of the major facilitative superfamily, generates uphill transport of folates into cells through an exchange mechanism with intracellular organic anions. RFC1 has twelve transmembrane domains with N- and C-termini, and the long loop connecting the 6th and 7th transmembrane domains, directed to the cytoplasm. To elucidate the role of the C-terminus and the long cytoplasmic loop in carrier function, mutants with deletion of the entire C-terminus or with progressive deletions of the loop region were constructed and stably transfected into the murine MTX(r)A cell line, which lacks functional RFC1. While expression of the C-terminus-deleted RFC1 protein could not be detected in the cell lysate, the RFC1 mutant lacking 57 of 66 amino acid residues of the long cytoplasmic loop appeared to be inserted into the cytoplasmic membrane but was not functional. In cell lines in which 17 or 31 amino acids were deleted from the carboxyl half of the loop, there was partial preservation of methotrexate, 5-formyltetrahydrofolate, and 5-methyltetrahydrofolate transport. The loss of 5-formyltetrahydrofolate transport activity in the delta31 and delta17 mutants was due primarily to a decrease in substrate binding to the carrier. Mutants with partially truncated internal loops demonstrated an anion responsiveness similar to that of wild-type RFC1, indicating that this region of the carrier does not contain a site(s) that plays a role in anion exchange. This is the first study to describe the important role of the long cytoplasmic loop in substrate binding and the crucial role of the C-terminus in maintaining stability of RFC1.

Amino Acid Sequence↗

PubMed2001

Metabolism of 10-formyldihydrofolate in humans.

The metabolism of 10-formyldihydrofolate is reviewed in this article. It had been the dogma that only tetrahydrofolates participate in enzyme-catalyzed one-carbon transfer reactions, until we showed in 1986 that 10-formyldihydrofolate serves as a substrate for aminoimidazolecarboxamide ribotide (AICAR) transformylase. Our data from studies in humans, cultured cells and bacteria as well as in vitro experiments indicate that the oxidation of 10-formyltetrahydrofolate to 10-formyldihydrofolate takes place, and 1 0-formyldihydrofolate is subsequently converted to dihydrofolate by AICAR transformylase. Dihydrofolate is then reduced to tetrahydrofolate and further metabolized by the well-established enzyme reactions. We believe that a new folate metabolic map is needed which incorporates the oxidation of 10-formyltetrahydrofolate and the utilization of 10-formyldihydrofolate by AICAR transformylase.

Bacteria↗

PubMed2001

Determination of folates in human plasma using hydrophilic interaction chromatography-tandem mass spectrometry.

Folic acid is an essential nutrient, and folate deficiency is associated with a variety of disorders including neural tube defects (during pregnancy) and heart disease. A fast, sensitive, and robust HPLC-tandem mass spectrometry (LC-MS-MS) method was developed for the quantification of free folic acid, tetrahydrofolate, 5'-methyltetrahydrofolate, and 5'-formyltetrahydrofolate in human plasma. Sample preparation required only acetonitrile precipitation of proteins followed by filtration instead of solid-phase extraction or solvent-solvent extraction as in other methods. The rapid and streamlined sample handling procedure minimized degradation of the highly unstable folate species. Hydrophilic interaction chromatography was used for additional sample cleanup on-line, and baseline separation and detection of all four folate species was achieved in less than 30 min. The folate species were detected using negative ion electrospray-tandem mass spectrometry with multiple reaction monitoring of the diagnostic fragment ions of each deprotonated molecule. The predominately organic (hydrophobic) solvent system combined with the microbore flow rate (50 microL/min) used for the chromatography resulted in enhanced electrospray signal response compared to reversed-phase HPLC using a wider bore column. The recovery of all folate species (from spiked plasma) was >97% over a concentration range from 300 pg/L to 12 mg/L with intraday precision (RSD, n = 5) of 3.7-6.5%. Stability studies were carried out for spiked samples in order to define storage and handling conditions. The folic acid limit of quantification (LOQ) in human plasma was 80 pmol/L +/- 10%, and the limit of detection (LOD) was 37.5 pmol/L. The LOQ and LOD for tetrahydrofolate, 5'-methyltetrahydrofolate, and 5'-formyltetrahydrofolate were 1250, 400, and 360 pmol/L of plasma and 425, 165, and 140 pmol/L of plasma, respectively.

Chromatography↗

PubMed2000

Human cytoplasmic serine hydroxymethyltransferase is an mRNA binding protein.

The 5' untranslated region (UTR) of the human cytoplasmic serine hydroxymethyltransferase (cSHMT) message is alternatively spliced, creating a full-length 5' UTR (LUTR) encoded within exons 1-3 and a shorter UTR (SUTR) that results from excision of exon 2. The role of the 5' UTRs in cSHMT expression was investigated by fusing the cSHMT 5' UTRs to the 5' end of the luciferase gene. Human cSHMT protein at 10 microM inhibits in vitro translation of cSHMT 5' UTR-luciferase fusion mRNA templates by more than 90%, but does not inhibit translation of the luciferase message lacking the UTR. Translation inhibition is independent of amino acid and folate substrate binding to the cSHMT enzyme. The cSHMT SUTR-luciferase mRNA binds to the cSHMT.glycine.5-formyltetrahydrofolate ternary complex with an apparent K(d) of 10 microM. Gel mobility shift assays demonstrate that the human cSHMT protein binds to the cSHMT LUTR-luciferase fusion mRNA in the presence and absence of glycine and 5-formyltetrahydrofolate pentaglutamate. The fusion cSHMT SUTR-luciferase message at 65 microM inhibits the cSHMT-catalyzed cleavage of allothreonine as a partial mixed type inhibitor, reducing both k(cat) and K(m) by 40 and 75%, respectively, while tRNA has no effect on cSHMT catalysis. These studies indicate that the cSHMT protein can bind mRNA, and displays increased affinity for the 5' untranslated region of its mRNA.

5' Untranslated Regions↗

PubMed1994

13C NMR analysis of intercompartmental flow of one-carbon units into choline and purines in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, the three-carbon of serine is normally the major one-carbon donor, although glycine and formate can substitute for serine. The second carbon of glycine enters via the glycine cleavage system in the mitochondria and can satisfy all cellular one-carbon requirements. It remains unresolved, however, as to the route by which these mitochondrial one-carbon units supply cytosolic anabolic processes. In the present work, we have used yeast mutants blocked at selected sites and 13C NMR to trace the incorporation of glycine-derived mitochondrial 5,10-methylenetetrahydrofolate into nonmitochondrial synthesis of choline and purines. Label incorporation into choline traces the methylation pathway of choline synthesis from production of serine to methylation of phosphatidylethanolamine. The active one-carbon unit of S-adenosylmethionine involved in methylation reactions originates almost solely from C3 of serine. On the other hand, flow of mitochondrial one-carbon units to 10-formyltetrahydrofolate for purine synthesis is shown to occur via both serine and formate. Formate transport accounts for at least 25% of the total, even during growth with sufficient serine to provide for the one-carbon requirements of the cell. This work shows that the synthetase function of the cytosolic C1-tetrahydrofolate synthase plays a critical role in the processing of mitochondrial one-carbon units to 10-formyltetrahydrofolate pools. In addition, this study provides evidence of two pools of glycine within the mitochondria and establishes a system of analyzing flux into the different folate derivatives.

Adenine↗

PubMed1984

Mammalian folyl polyglutamate synthetase: partial purification and properties of the mouse liver enzyme.

Folyl polyglutamate synthetase has been partially purified from mouse liver, and the general features of this enzyme have been characterized. The purification procedure utilized fractionation with ammonium sulfate, gel filtration, and affinity chromatography on ATP-agarose and resulted in a 350-fold increase in specific activity with 8-20% recovery of enzyme activity. Enzyme could be stabilized by glycerol or by ATP, but stability was not appreciably enhanced by folate. The enzymatic reaction was completely dependent on folate, ATP, and Mg2+ while partial reaction rates were observed in the absence of KCl or beta-mercaptoethanol. Highest reaction rates were observed at pH 8.2-9.5 at 37 degrees C. Chromatography of purified enzyme on calibrated gel filtration columns suggested a molecular weight of 65 000. Mouse liver folyl polyglutamate synthetase coupled [3H]glutamic acid to all of the naturally occurring folates studied. Analysis of the reaction products by high-performance liquid chromatography demonstrated that several folyl oligoglutamates were formed at low substrate concentrations but that only folyl diglutamate was formed at substrate concentrations approaching saturation. Dihydrofolate, tetrahydrofolate, 5,10-methylenetetrahydrofolate, 10-formyltetrahydrofolate, and 5-formyltetrahydrofolate were the best substrates. Folic acid and 5-methyltetrahydrofolate were also substrates for this reaction, but much higher concentrations of these compounds were required to saturate the enzyme. These data suggest that all of the tetrahydrofolyl compounds (except 5-methyltetrahydrofolate) are the monoglutamyl substrates for polyglutamation in vivo and that 5-methyltetrahydrofolate is not likely to be a direct precursor for folate polyglutamates in mouse liver.

Animals↗

PubMed1987

Interaction of tetrahydrofolate and other folate derivatives with bacterial sarcosine oxidase.

Sarcosine oxidase from Corynebacterium sp. P-1 binds 2 mol of tetrahydrofolate/mol of enzyme (KD = 8.8 microM). The same stoichiometry is observed with tetrahydropteroyltetraglutamate (KD = 15.4 microM). Binding is also observed with pteroyltetraglutamate and with 5-formyltetrahydrofolate. In the case of the pteroylmonoglutamates, binding appears to be sensitive to changes in the pteridine ring since no binding is observed with 5-methyltetrahydrofolate or with folate. Sarcosine oxidase can be specifically adsorbed onto an affinity matrix prepared by coupling 5-formyltetrahydrofolate to AH-Sepharose. Tetrahydrofolate does not affect the rate of sarcosine oxidation but does block the formation of formaldehyde as a final product. In the presence of tetrahydrofolate, sarcosine oxidation is accompanied by the formation of 5,10-methylenetetrahydrofolate at a rate that exceeds the rate at which formaldehyde (or a precursor) can be released into solution and which is also considerably faster than the nonenzymic reaction of free formaldehyde with tetrahydrofolate. It is suggested that tetrahydrofolate may serve primarily to trap formaldehyde as it is formed at the active site during sarcosine oxidation. The existence of a catalytically significant binding site for tetrahydrofolate appears to be a general property of sarcosine oxidizing enzymes since similar results have previously been obtained with mammalian sarcosine dehydrogenase, an enzyme that is structurally and mechanistically very different from bacterial sarcosine oxidase.

Aldehyde Oxidoreductases↗

PubMed1989

Reconstitution of Escherichia coli DNA photolyase with various folate derivatives.

DNA photolyase from Escherichia coli contains both flavin and pterin. However, the isolated enzyme is depleted with respect to the pterin chromophore (0.5 mol of pterin/mol of flavin). The extinction coefficient of the pterin chromophore at 360 nm is underestimated by a method used in earlier studies which assumes stoichiometric amounts of pterin and flavin. The extinction coefficient of the pterin chromophore, determined on the basis of its (p-aminobenzoyl)polyglutamate content (epsilon 360 = 25.7 x 10(3) M-1 cm-1), is in good agreement with that expected for a 5,10-methenyltetrahydrofolate derivative. Also consistent with this structure, the pterin chromophore could be reversibly hydrolyzed to yield a 10-formyltetrahydrofolate derivative or reduced to yield a 5-methyltetrahydrofolate derivative. The isolated enzyme could be reconstituted with various folate derivatives to yield enzyme that contained equimolar amounts of pterin and flavin. Similar results were obtained in reconstitution studies with the natural pterin chromophore, with 5,10-methenyltetrahydrofolate, and with 10-formyltetrahydrofolate. The results show that the polyglutamate moiety, previously identified in the natural chromophore, is not critical for binding. Reconstitution with the natural pterin chromophore did not affect catalytic activity. The latter is consistent with our previous studies which show that, although the pterin chromophore acts as a sensitizer in native enzyme, it is not essential for dimer repair which can occur at the same rate under saturating light with flavin (1,5-dihydro-FAD) as the only chromophore.

Deoxyribodipyrimidine Photo-Lyase↗

PubMed1981

On the purification and mechanism of action of 5-aminoimidazole-4-carboxamide-ribonucleotide transformylase from chicken liver.

The transformylase from chicken liver catalyzing the formylation of 5-aminoimidazole-4-carboxamide ribonucleotide through the agency of 19-formyltetrahydrofolate has been purified to apparent homogeneity. Inosinicase activity copurifies. This transformylase is not further activated kinetically by the presence of the trifunctional protein in contrast to the glycinamide ribonucleotide transformylase. The enzyme exhibits a greater than 1000-fold preference for the naturally occurring 10-formyltetrahydrofolate cofactor and a sequential reaction pattern. A reinvestigation of the chemical structure of the formylated ribotide product employing 13C and 1H NMR indicated that the imidazole ring remained intact upon formylation, consistent with the originally proposed structure.

Acyltransferases↗

PubMedDate not supplied

C-formylation in the presence of rat brain mitochondria of the 2,3,4,5-tetrahydropyridinium metabolite derived from the psychotomimetic drug phencyclidine.

The 1-(1-phenylcyclohexyl)-2,3,4,5-tetrahydropyridinium metabolite derived from the psychotomimetic agent phencyclidine [1-(1-phenylcyclohexyl)piperidine] is converted to 1-(phenylcyclohexyl)-1,2,3,4-tetrahydropyridine-5-carboxaldehyde in the presence of rat brain and liver mitochondria. The C-5 formylation of synthetic 1-(1-phenylcyclohexyl)-2,3,4,5-tetrahydropyridinium perchlorate by N5-formyltetrahydrofolic acid (folinic acid) suggests that this biotransformation is mediated by a transformylation process involving this N5- or the corresponding N10-formyltetrahydrofolic acid.

Animals↗