The Enzymatic Formation of Formiminotetrahydrofolic Acid, 5,10-Methenyltetrahydrofolic Acid, and 10-Formyltetrahydrofolic Acid in the Metabolism of Formiminoglutamic Acid

Tabor, Herbert; Wyngarden, Lillian J.

doi:10.1016/s0021-9258(18)69935-1

Cited by 157 publications

(13 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The chemical conversions of 5-HCO-H % F into 5,10-CHH % F and 5,10-CHH % F into 10-HCO-H % F have been well documented. These reactions should take place in the acidic environment of the stomach and the neutral pH environment of the upper small intestine or the cellular cytoplasm, respectively (Figure 1) [4,[31][32][33]. The rapid in i o oxidation of 10-HCO-H % F to 10-HCO-H # F is not so readily explained.…”

Section: Discussionmentioning

confidence: 99%

“…The C-6 optical isomer, [6R ]-5-formyl-5,6,7,8-tetrahydrofolate (5-HCO-H % F), is a chemically synthesized compound, not found in living organisms [1,2]. [6R ]-5-HCO-H % F and its C-6 configurationally related folates are not utilized by folate-requiring bacteria or by enzymes of folate metabolism since these enzymes recognize only the naturally occurring isomer, [6S ]-5-HCO-H % F, and its C-6 configurationally related folates [3][4][5][6][7][8][9][10][11][12][13]. Therefore, [6R ]-5-HCO-H % F was used here as a tool to uncover possible ' chemical metabolism ' of this folate and its C-6 configurationally related folates in living organisms.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Bioactivity of [6R]-5-formyltetrahydrofolate, an unnatural isomer, in humans and Enterococcus hirae, and cytochrome c oxidation of 10-formyltetrahydrofolate to 10-formyldihydrofolate

2001

View full text Add to dashboard Cite

The bio-inactive C-6 isomer, [6R]-5-formyl-tetrahydrofolate (5-HCO-H(4)F), is not found in Nature. An oral dose of 13.5 micromol of [6R]-5-HCO-H(4)F in humans results in the appearance of the naturally occurring [6S]-5-methyl-tetrahydrofolate and relatively large amounts of other bioactive folates in plasma. The removal of the asymmetry at C-6 could account for these results. Two oxidized cytochrome c [cyt c (Fe3+)] molecules oxidize one 10-formyl-tetrahydrofolate (10-HCO-H(4)F) with second-order kinetics and a rate constant of 1.3 x 10(4) M(-1) x s(-1). The folate product of this oxidation reaction is 10-formyl-dihydrofolate (10-HCO-H(2)F), which has no C-6 asymmetric centre and is therefore bioactive. The folate-requiring bacterium, Enterococcus hirae, does not normally biosynthesize cytochromes but does so when given an exogenous source of haem (e.g. haemin). E. hirae grown in haemin-supplemented media for 3 days utilizes both [6R]- and [6S]-5-HCO-H(4)F in contrast to that grown in control medium, which utilizes only the [6S] isomer. Since known chemical reactions form 10-HCO-H(4)F from 5-HCO-H(4)F, the unusually large rate constant for the oxidation of 10-HCO-H(4)F by cyt c (Fe3+) may account for the unexpected bioactivity of [6R]-5-HCO-H(4)F in humans and in E. hirae grown in haemin-containing media. We used an unnatural C-6 folate isomer as a tool to reveal the possible in vivo oxidation of 10-HCO-H(4)F to 10-HCO-H(2)F; however, nothing precludes this oxidation from occurring in vivo with the natural C-6 isomer.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bioactivity of [6R]-5-formyltetrahydrofolate, an unnatural isomer, in humans and Enterococcus hirae, and cytochrome c oxidation of 10-formyltetrahydrofolate to 10-formyldihydrofolate

2001

View full text Add to dashboard Cite

show abstract

“…Hydrochloride. The native transferase-deaminase is stabilized or activated by both monovalent cations and polyvalent anions (Tabor & Wyngarden, 1959;Drury et al" 1975) and is clearly less stable in the absence of potassium and phosphate. Dissociation of the enzyme by urea in TEA-HC1 buffer proceeds by a different sequence from that seen in potassium phosphate, with dissociation to dimers and preferential retention of the transferase activity in only 1 M urea.…”

Section: Production Of Two Types Of Dimer In Triethanolaminementioning

confidence: 99%

Dissociation of the octameric bifunctional enzyme formiminotransferase-cyclodeaminase in urea. Isolation of two monofunctional dimers

Findlay¹,

MacKenzie²

1987

Biochemistry

View full text Add to dashboard Cite

Partial denaturation of the circular octameric bifunctional enzyme formiminotransferase-cyclodeaminase in increasing urea concentrations leads to sequential dissociation via dimers to inactive monomers. In potassium phosphate buffer, dissociation to dimers in 3 M urea coincides with loss of both activities and a major decrease in intensity of intrinsic tryptophan fluorescence. In the presence of folic acid, these dimers retain the deaminase activity, but with folylpolyglutamates, both activities are protected and the native octameric structure is retained. The protection profiles with polyglutamates are cooperative with a Hill coefficient greater than 2, suggesting that binding of more than one folylpolyglutamate per octamer is required to stabilize the native structure. In triethanolamine hydrochloride buffer, transferase-active dimers that retain the intrinsic tryptophan fluorescence can be obtained in 1 M urea and stabilized at higher urea concentration by the addition of glutamate. Deaminase-active dimers are obtained by the protection of folate in 3 M urea. Proteolysis of the two kinds of dimers by chymotrypsin leads to very different fragmentation patterns, indicating that they are structurally different. We propose that the two dimers retain different subunit-subunit interfaces, one of which is required for each activity. This suggests that the native octameric structure is required for expression of both activities and therefore for "channeling" of intermediates.

show abstract

“…The Michaelis constant, Km, for UMP (2.7 X 10~5m) and UDP-MurNAc-pentapeptide (1.8 X 10~6 m) had been established with membranes that were washed in 0.005 m Tris-HCl (pH 7.8) containing 1 m KC1 (Struve et al, 1966). Since K+ has been shown to affect the Umax and Michaelis-Menten constants of several enzymes (Neuhaus, 1962; Edwards and Keech, 1968; Tabor and Wyngarden, 1959;Marshall et al, 1961;Giorgio and Plaut, 1967;Bright, 1967;Robinson, 1967Robinson, , 1969Nandi et al, 1968), the effects of UMP and UDP-MurNAc-pentapeptide on the exchange assay in the presence of several concentrations of K+ were examined. In the case of UMP (Figure 5A and Table II),…”

Section: Resultsmentioning

confidence: 99%

Initial stage in peptidoglycan synthesis. 5. Mechanism of activation of phospho-N-acetylmuramyl-pentapeptide translocase by potassium ions

Heydanek¹,

Linzer²,

Pless³

et al. 1970

Biochemistry

View full text Add to dashboard Cite

The initial reaction in the biosynthesis of peptidogiycan is catalyzed by phospho-A^-acetylmuramyl-pentapeptide translocase (UDP-MurNAc-L-Ala-D-7-Glu-L-Lys-D-Ala-o-Ala: C56-isoprenoid alcohol phosphate phospho-MurNAc-pentapeptide transferase). In addition to the transfer reaction, the enzyme catalyzes the exchange of [8H]uridine monophosphate with the uridine monophosphate moiety of UDP-MurNAc-pentapeptide. In addition to an absolute requirement for Mg2+, the translocase is stimulated by either K+, NH4+, Rb+, or Cs+. Addition of K+ (0.17 m) to dialyzed membranes stimulates the exchange reaction 20-fold and the transfer reaction 2-fold. The stimulation by K+ gives a normal hyperbolic saturation curve with a Michaelis-Menten constant of 0.01 m in the exchange reaction. The value for (1) established from Hill plots suggests the absence of homotropic effects and that a single binding site for K+ exists in T Xhe biosynthesis of peptidoglycan, the major structura' heteropolymer of bacterial cell walls, is catalyzed by a series of enzymes associated with the bacterial membrane (Anderson

show abstract

The Enzymatic Formation of Formiminotetrahydrofolic Acid, 5,10-Methenyltetrahydrofolic Acid, and 10-Formyltetrahydrofolic Acid in the Metabolism of Formiminoglutamic Acid

Cited by 157 publications

References 33 publications

Bioactivity of [6R]-5-formyltetrahydrofolate, an unnatural isomer, in humans and Enterococcus hirae, and cytochrome c oxidation of 10-formyltetrahydrofolate to 10-formyldihydrofolate

Bioactivity of [6R]-5-formyltetrahydrofolate, an unnatural isomer, in humans and Enterococcus hirae, and cytochrome c oxidation of 10-formyltetrahydrofolate to 10-formyldihydrofolate

Dissociation of the octameric bifunctional enzyme formiminotransferase-cyclodeaminase in urea. Isolation of two monofunctional dimers

Initial stage in peptidoglycan synthesis. 5. Mechanism of activation of phospho-N-acetylmuramyl-pentapeptide translocase by potassium ions

Contact Info

Product

Resources

About