The Identification of Hexa-, Hepta- and Octoglutamates as the Polyglutamyl Forms of Folate Found throughout the Growth Cycle of Yeast

Bassett, Ray; Weir, D. G.; Scott, John M.

doi:10.1099/00221287-93-1-169

Cited by 28 publications

(6 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This region has 12 basic residues and may be involved in the binding of the polyglutamyl forms of folate coenzymes found in vivo. The predominant forms of folate coenzymes in S. cerevisiae contain six to eight glutamyl residues, with the heptaglutamyl form being the major component (4). In contrast, the folate coenzymes in C. acidiurici occur exclusively as triglutamate derivatives (9,29), and the enzyme may not require such an extensive region of basic amino acids to recognize these derivatives.…”

Section: Figmentioning

confidence: 99%

“…Therefore, it is more likely that P1 is used for initiation by the RNA polymerase. It is interesting to note that the synthetase comprises about 4 to 5% of the C. acidiurici cellular protein (36) and that only one gene copy is apparent in the chromosome (41). Therefore, the gene is probably strongly expressed in the cell, and the dual promoter elements may enhance the expression of the gene.…”

Section: Figmentioning

confidence: 99%

See 1 more Smart Citation

Nucleotide sequence of the Clostridium acidiurici ("Clostridium acidi-urici") gene for 10-formyltetrahydrofolate synthetase shows extensive amino acid homology with the trifunctional enzyme C1-tetrahydrofolate synthase from Saccharomyces cerevisiae

Whitehead

Rabinowitz

1988

J Bacteriol

View full text Add to dashboard Cite

The nucleotide sequence of the gene for 10-formyltetrahydrofolate synthetase (EC 6.3.4.3) from Clostridium acidiurici ("Clostridium acidi-urici") was determined. The synthetase mRNA initiation and termination regions were determined by primer extension and Si nuclease mapping. Two potential -10 and -35 promoter regions were identified upstream of mRNA initiation. The terminator region was found to be in a large region of dyad symmetry. A comparison of the amino acid sequences of the monofunctional synthetase and the eucaryotic trifunctional enzyme, C1-tetrahydrofolate synthase, from Saccharomyces cerevisiae demonstrated a region of strong homology.

show abstract

Section: Figmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

Nucleotide sequence of the Clostridium acidiurici ("Clostridium acidi-urici") gene for 10-formyltetrahydrofolate synthetase shows extensive amino acid homology with the trifunctional enzyme C1-tetrahydrofolate synthase from Saccharomyces cerevisiae

Whitehead

Rabinowitz

1988

J Bacteriol

View full text Add to dashboard Cite

show abstract

“…The production of HGH could be visualized on a Western blot using polyclonal anti-␥-glutamyl hydrolase antibody (results not shown). The HGH expression and activity in L. lactis was tested on yeast extract containing mostly heptaglutamyl folate (1). Figure 3 shows the progressive deconjugation of polyglutamyl folate in yeast extract by a cell extract of L. lactis NZ9000 harboring pNZ7001 induced with 1 ng of nisin/ml.…”

Section: Vol 69 2003 Control Of Folate Polyglutamyl Tail Length In mentioning

confidence: 99%

ControlledModulation of Folate Polyglutamyl Tail Length by Metabolic Engineeringof Lactococcuslactis

Sybesma

Born

Starrenburg

et al. 2003

Appl Environ Microbiol

View full text Add to dashboard Cite

The dairy starter bacterium Lactococcus lactis is able to synthesize folate and accumulates >90% of the produced folate intracellularly, predominantly in the polyglutamyl form. Approximately 10% of the produced folate is released into the environment. Overexpression of folC in L. lactis led to an increase in the length of the polyglutamyl tail from the predominant 4, 5, and 6 glutamate residues in wild-type cells to a maximum of 12 glutamate residues in the folate synthetase overproducer and resulted in a complete retention of folate in the cells. Overexpression of folKE, encoding the bifunctional protein 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase and GTP-cyclohydrolase I, resulted in reduction of the average polyglutamyl tail length, leading to enhanced excretion of folate. By simultaneous overexpression of folKE and folC, encoding the enzyme folate synthetase or polyglutamyl folate synthetase, the average polyglutamyl tail length was increased, again resulting in normal wild-type distribution of folate. The production of bioavailable monoglutamyl folate and almost complete release of folate from the bacterium was achieved by expressing the gene for ␥-glutamyl hydrolase from human or rat origin. These engineering studies clearly establish the role of the polyglutamyl tail length in intracellular retention of the folate produced. Also, the potential application of engineered food microbes producing folates with different tail lengths is discussed.

show abstract

“…At that time it was still unclear whether the conjugates were the major coenzyme forms of folate in cells or were simply storage forms. In studies of the cell cycle in yeast (Bassett et al , ) he showed that polyglutamates were the dominant forms in proliferating as well as in resting cells. This is also the case for mammalian cells (Lavoie et al , ), implying that the polyglutamate forms are involved as coenzymes in DNA synthesis, subsequently shown by others in direct enzyme kinetic studies in which the polyglutamates showed enhanced activity in various folate mediated reactions compared to the monoglutamate forms.…”

Section: Early Researchmentioning

confidence: 99%

Professor John Scott, folate and neural tube defects

Hoffbrand

2013

Br J Haematol

View full text Add to dashboard Cite

SummaryJohn Scott (1940Scott ( -2013 was born in Dublin where he was to spend the rest of his career, both as an undergraduate and subsequently Professor of Biochemistry and Nutrition at Trinity College. His research with the talented group of scientists and clinicians that he led has had a substantial impact on our understanding of folate metabolism, mechanisms of its catabolism and deficiency. His research established the leading theory of folate involvement with vitamin B12 in the pathogenesis of vitamin B12 neuropathy. He helped to establish the normal daily intake of folate and the increased requirements needed either in food or as a supplement before and during pregnancy to prevent neural tube defects. He also suggested a dietary supplement of vitamin B12 before and during pregnancy to reduce the risk of neural tube defects. It would be an appropriate epitaph if fortification of food with folic acid became mandatory in the UK and Ireland, as it is in over 70 other countries.

show abstract

The Identification of Hexa-, Hepta- and Octoglutamates as the Polyglutamyl Forms of Folate Found throughout the Growth Cycle of Yeast

Cited by 28 publications

References 4 publications

Nucleotide sequence of the Clostridium acidiurici ("Clostridium acidi-urici") gene for 10-formyltetrahydrofolate synthetase shows extensive amino acid homology with the trifunctional enzyme C1-tetrahydrofolate synthase from Saccharomyces cerevisiae

Nucleotide sequence of the Clostridium acidiurici ("Clostridium acidi-urici") gene for 10-formyltetrahydrofolate synthetase shows extensive amino acid homology with the trifunctional enzyme C1-tetrahydrofolate synthase from Saccharomyces cerevisiae

ControlledModulation of Folate Polyglutamyl Tail Length by Metabolic Engineeringof Lactococcuslactis

Professor John Scott, folate and neural tube defects

Contact Info

Product

Resources

About