A Labile Precursor of Citrovorum Factor

Nichol, Charles A.; Anton, Aaron H.; Zakrzewski, Sigmund F.

doi:10.1126/science.121.3139.275

Cited by 34 publications

(10 citation statements)

References 23 publications

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“…This designation as the "de novo pathway" refers to the steps in the endogenous biosynthesis of the active cofactor from nonpterin precursors, a process that is dependent upon purine nucleotide biosynthesis and the availability of guanosine, GMP, and GTP. Our present understanding of biopterin cofactor biosynthesis is comparable to when labile uncharacterized forms of the folate cofactors were converted to stable 5-formyltetrahydrofolate (31). The present evidence indicates that sepiapterin is converted to BH4 by a MTX-sensitive pathway.…”

supporting

confidence: 63%

Biosynthesis of tetrahydrobiopterin by de novo and salvage pathways in adrenal medulla extracts, mammalian cell cultures, and rat brain in vivo.

Nichol¹,

Lee²,

Edelstein³

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

107

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Communicated by George H. Hitchings, December 13, 1982 ABSTRACT Mammalian cells and tissues were found to have two pathways for the biosynthesis of tetrahydrobiopterin (BH4): (i) the conversion of GTP to BH4 by a methotrexate-insensitive de novo pathway, and (ii) the conversion of sepiapterin to BH4 by a pterin salvage pathway dependent on dihydrofolate reductase (5,6,7,8-tetrahydrofolate:NADP+ oxidoreductase, EC 1.5.1.3) activity. In a Chinese hamster ovary cell mutant lacking dihydrofolate reductase (DUKX-BII), endogenous formation of BH4 proceeds normally but, unlike the parent cells, these cells or extracts ofthem do not convert sepiapterin or 7,8-dihydrobiopterin to BH4. KB cells, which do not contain detectable levels of GTP cyclohydrolase or BH4 but do contain dihydrofolate reductase, readily convert sepiapterin to BH4 and this conversion is completely prevented by methotrexate. In supernatant fractions of bovine adrenal medulla, the conversion of sepiapterin to BH4 is completely inhibited by methotrexate. Similarly, this conversion in rat brain in vivo is methotrexate-sensitive. Sepiapterin and 7,8-dihydrobiopterin apparently do not enter the de novo pathway of BH4 biosynthesis and may be derived from labile intermediates which have not yet been characterized.

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supporting

confidence: 63%

Biosynthesis of tetrahydrobiopterin by de novo and salvage pathways in adrenal medulla extracts, mammalian cell cultures, and rat brain in vivo.

Nichol¹,

Lee²,

Edelstein³

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

107

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“…The data are based on the growth of inocula (10 mg dry weight/inoculum) incubated for 8 days in 1.5 liters of CO2-aerated liquid media. The response to folic acid is not surprising in view of the evidence that the biological activity of PABA depends on its incorporation into the ptereie acid portion of folic acid (Welch and Nichol, 1952;Nichol, Anton, and Zakrzewski, 1955). number of 27 for P. patens collected in Michigan.…”

Section: Mutation Induction-spores and Protonemal Cells Were Irradiatmentioning

confidence: 99%

The Induction of Biochemical and Morphological Mutants in the Moss Physcomitrella Patens

Engel

1968

American J of Botany

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Physcomitrella patens is a monoecious, cleistocarpous moss which completes its life cycle under defined conditions in 7 to 8 weeks. Sexual reproduction is readily obtained by culturing gametophytes at 15 to 19 C. Mutants were induced by treatment of either spores or protonemal cells with ethyl methane sulfonate, N‐methyl‐N'‐nitro‐N‐nitrosoguanidine and X‐rays. Thiamine, para‐aminobenzoic acid, niacin and yeast extract auxotrophs were obtained. Growth response to various supplements was studied in the auxotrophic mutants. Five yellow mutants and two morphological mutants were induced. The chlorophyll content of the yellow mutants is reduced 35‐65% of wild type. The self‐sterile, para‐aminobenzoic acid‐dependent mutant was used as the archegonial parent in crosses with a yellow mutant and a morphological mutant. The self‐sterility of the para‐aminobenzoic acid‐requiring mutant appears to be pleiotropically related to the auxotrophic condition, since self‐sterility does not segregate from nutritional dependence in progeny of crosses. On the basis of tests with heterozygous diploids obtained by aposporous regeneration of capsule cells, two mutant alleles were shown to be recessive to their respective wild‐type alleles.

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“…Recent evidence has shown that a heat-labile precursor of citrovorum factor is converted to a stable form of citrovorum factor by autoclaving in the presence of ascorbic acid (Silverman et al, 1956;Nichol et al, 1955). Such a treatment was used in the citrovorum factor assays of N. crassa.…”

Section: Methodsmentioning

confidence: 99%

STUDY OF FOLIC ACID DERIVATIVES IN NEUROSPORA CRASSA AND THE RECOGNITION OF A MUTANT RESISTANT TO AMINOPTERIN

Swendseid

Nyc

1958

J Bacteriol

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A Labile Precursor of Citrovorum Factor

Cited by 34 publications

References 23 publications

Biosynthesis of tetrahydrobiopterin by de novo and salvage pathways in adrenal medulla extracts, mammalian cell cultures, and rat brain in vivo.

Biosynthesis of tetrahydrobiopterin by de novo and salvage pathways in adrenal medulla extracts, mammalian cell cultures, and rat brain in vivo.

The Induction of Biochemical and Morphological Mutants in the Moss Physcomitrella Patens

STUDY OF FOLIC ACID DERIVATIVES IN NEUROSPORA CRASSA AND THE RECOGNITION OF A MUTANT RESISTANT TO AMINOPTERIN

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