An endogenous inhibitor of folylpolyglutamate synthetase in Neurospora crassa

Cossins, Edwin A.; Chan, Patrick Y.

doi:10.1016/0031-9422(88)80737-4

Cited by 7 publications

(6 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In other organisms, lack of compartmentalised polyglutamylation leads to a range of metabolic and phenotypic defects (Sussman et al. , 1986; Cossins and Chan, 1988; Pyne and Bognar, 1992; Lin et al. , 1993; Liu et al.…”

Section: Discussionmentioning

confidence: 99%

“…In other organisms, lack of compartmentalised polyglutamylation leads to a range of metabolic and phenotypic defects (Sussman et al, 1986;Cossins and Chan, 1988;Pyne and Bognar, 1992;Lin et al, 1993;Cherest et al, 2000;DeSouza et al, 2000). It was therefore surprising that the loss of organelle-specific FPGS isoforms in Arabidopsis single FPGS mutant lines did not result in the anticipated auxotrophic phenotypes.…”

Section: One or More Fpgs Gene Products Have A Degree Of Functional Rmentioning

confidence: 99%

“…The physiological importance of folate polyglutamylation in animals and micro‐organisms has been demonstrated by genetic studies in which disruption of FPGS activity led to auxotrophy for the end‐products of C 1 metabolism (Sussman et al. , 1986; Cossins and Chan, 1988; Pyne and Bognar, 1992; Lin et al. , 1993; Liu et al.…”

Section: Introductionmentioning

confidence: 99%

“…The physiological importance of folate polyglutamylation in animals and micro-organisms has been demonstrated by genetic studies in which disruption of FPGS activity led to auxotrophy for the end-products of C 1 metabolism (Sussman et al, 1986;Cossins and Chan, 1988;Pyne and Bognar, 1992;Lin et al, 1993;Cherest et al, 2000;DeSouza et al, 2000). These defects are attributable to decreased co-factor affinity/ functions in folate-dependent reactions, and emphasise that the folate polyglutamylation status of an organism is central to folate homeostasis.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Functional analysis of folate polyglutamylation and its essential role in plant metabolism and development

et al. 2010

View full text Add to dashboard Cite

SUMMARYCellular folates function as co-enzymes in one-carbon metabolism and are predominantly decorated with a polyglutamate tail that enhances co-enzyme affinity, subcellular compartmentation and stability. Polyglutamylation is catalysed by folylpolyglutamate synthetases (FPGSs) that are specified by three genes in Arabidopsis, FPGS1, 2 and 3, which reportedly encode plastidic, mitochondrial and cytosolic isoforms, respectively. A mutational approach was used to probe the functional importance of folate polyglutamylation in one-carbon metabolism and development. Biochemical analysis of single FPGS loss-of-function mutants established that folate polyglutamylation is essential for organellar and whole-plant folate homeostasis. However, polyglutamylated folates were still detectable, albeit at lower levels, in organelles isolated from the corresponding isozyme knockout lines, e.g. in plastids and mitochondria of the fpgs1 (plastidial) and fpgs2 (mitochondrial) mutants. This result is surprising given the purported single-compartment targeting of each FPGS isozyme. These results indicate redundancy in compartmentalised FPGS activity, which in turn explains the lack of anticipated phenotypic defects for the single FPGS mutants. In agreement with this hypothesis, fpgs1 fpgs2 double mutants were embryo-lethal, fpgs2 fpgs3 mutants exhibited seedling lethality, and fpgs1 fpgs3 mutants were dwarfed with reduced fertility. These phenotypic, metabolic and genetic observations are consistent with targeting of one or more FPGS isozymes to multiple organelles. These data confirm the importance of polyglutamylation in folate compartmentation, folate homeostasis and folate-dependent metabolic processes, including photorespiration, methionine and pantothenate biosynthesis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: One or More Fpgs Gene Products Have A Degree Of Functional Rmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Functional analysis of folate polyglutamylation and its essential role in plant metabolism and development

et al. 2010

View full text Add to dashboard Cite

show abstract

“…110 In Neurospora crassa, mutation at the met-9 locus results in FPGS inhibition and auxotrophy for methionine, an observation that emphasizes the importance of the polyglutamate derivatives. 111 Likewise, a DHFR-de®cient mutant of Saccharomyces cerevisiae has auxotrophic growth requirements for the products of the C1 metabolism such as methionine, adenine, dTMP. 112 Two steps of the tetrahydrofolate synthesis pathway are of great medical interest.…”

Section: Mutantsmentioning

confidence: 99%

Folic acid and folates: the feasibility for nutritional enhancement in plant foods

Scott¹,

Rébeillé²,

Fletcher³

2000

J. Sci. Food Agric.

View full text Add to dashboard Cite

In mammalian and plant cells the folates play a key role in the methylation cycle and in the DNA biosynthesis cycle (in the de novo biosynthesis of purines and pyrimidines). De®ciency of folate in the diet is likely to result in a reduction in the capacity to synthesise DNA and maintain the usual rate of cell division. This most evidently results in the production of anaemia from folate de®ciency due to a reduction in the biosynthesis of cells in the bone marrow. In addition it has been shown that high levels of plasma homocysteine occur which is an important risk factor in cardiovascular disease. Furthermore it has been shown that reduced maternal folate status is associated with the progressive increase in neural tube defects in infants. There is good evidence for folate de®ciency in a considerable number of the population in developed countries, even where folate supplementation of foods is practised, and for a level of intake in excess of the recommended dietary allowance. This paper reviews the principal routes of folate biosynthesis in plants and the potential for increasing the levels of natural folates through conventional plant breeding and biotechnological means. The effect of the major food preservation processes on the levels of folates in plants is also reviewed. The current information about the bioavailability of folates from plant food sources, and how this might be improved, is also summarised. The important health bene®ts that would arise from increasing folate intake in the diet provide a strong incentive for considering how this might be achieved.

show abstract

Folic acid and folates: the feasibility for nutritional enhancement in plant foods

Scott¹,

Rébeillé²,

Fletcher³

2000

J. Sci. Food Agric.

289

237

View full text Add to dashboard Cite

In mammalian and plant cells the folates play a key role in the methylation cycle and in the DNA biosynthesis cycle (in the de novo biosynthesis of purines and pyrimidines). Deficiency of folate in the diet is likely to result in a reduction in the capacity to synthesise DNA and maintain the usual rate of cell division. This most evidently results in the production of anaemia from folate deficiency due to a reduction in the biosynthesis of cells in the bone marrow. In addition it has been shown that high levels of plasma homocysteine occur which is an important risk factor in cardiovascular disease. Furthermore it has been shown that reduced maternal folate status is associated with the progressive increase in neural tube defects in infants. There is good evidence for folate deficiency in a considerable number of the population in developed countries, even where folate supplementation of foods is practised, and for a level of intake in excess of the recommended dietary allowance. This paper reviews the principal routes of folate biosynthesis in plants and the potential for increasing the levels of natural folates through conventional plant breeding and biotechnological means. The effect of the major food preservation processes on the levels of folates in plants is also reviewed. The current information about the bioavailability of folates from plant food sources, and how this might be improved, is also summarised. The important health benefits that would arise from increasing folate intake in the diet provide a strong incentive for considering how this might be achieved. © 2000 Society of Chemical Industry

show abstract

An endogenous inhibitor of folylpolyglutamate synthetase in Neurospora crassa

Cited by 7 publications

References 46 publications

Functional analysis of folate polyglutamylation and its essential role in plant metabolism and development

Functional analysis of folate polyglutamylation and its essential role in plant metabolism and development

Folic acid and folates: the feasibility for nutritional enhancement in plant foods

Folic acid and folates: the feasibility for nutritional enhancement in plant foods

Contact Info

Product

Resources

About