The effects of folate intake on DNA and single-carbon pathway metabolism in the fruit fly Drosophila melanogaster compared to mammals

Sydella A. Blatch, Sally P. Stabler, Jon Harrison

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Mechanisms of vitamin function in non-mammals are poorly understood, despite being essential for development. Folate and cobalamin are B-vitamin cofactors with overlapping roles in transferring various single-carbon units. In mammals, one or both is needed for nucleotide synthesis, DNA methylation, amino acid conversions and other reactions. However, there has been little investigation of the response to folate or cobalamin in insects. Here, we manipulated folate intake and potentially cobalamin levels in the fruit fly Drosophila melanogaster with chemically-defined diets, an antibiotic to reduce bacterially-derived vitamins, and the folate-interfering pharmaceutical methotrexate, to see if single-carbon metabolites and DNA synthesis rates would be affected. We found that similar to mammals with low folate intake, fruit fly larvae had significantly slower growth and DNA synthesis rates. But changes to single carbon-metabolites did not mirror that of mammals with abnormal folate or given MTX. Five of the nine metabolites measured were not significantly affected (methionine, serine, glycine, methylglycine, and dimethylglycine) and three (cystathionine, methylgycine, and methylmalonic acid) were only decreased in larvae consuming methotrexate. Metabolites expected to be elevated if flies used cobalamin from microbial symbionts were not affected by dietary sulfaquinoxaline. Our data support the role of folate in nucleotide synthesis in D. melanogaster and that microbial symbionts provide functioning folates. We could not confirm how folate intake affects single carbon pathway metabolites, nor whether Drososphila use microbially-derived cobalamin. Further work should explore which cofactors are used in fruit flies in these important and potentially novel pathways.

Original languageEnglish (US)
Pages (from-to)34-39
Number of pages6
JournalComparative Biochemistry and Physiology Part - B: Biochemistry and Molecular Biology
Volume189
DOIs
StatePublished - Nov 1 2015

Fingerprint

Mammals
Fruits
Drosophila melanogaster
Folic Acid
Metabolism
Diptera
Fruit
Carbon
Vitamin B 12
Metabolites
DNA
Methotrexate
Vitamins
Larva
Sulfaquinoxaline
Nucleotides
Methylmalonic Acid
Cystathionine
Sarcosine
Conversion Disorder

Keywords

  • Bacteria
  • Insect
  • Sulfaquinoxaline
  • Transsulfuration
  • Vitamin B-12

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Physiology

Cite this

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title = "The effects of folate intake on DNA and single-carbon pathway metabolism in the fruit fly Drosophila melanogaster compared to mammals",
abstract = "Mechanisms of vitamin function in non-mammals are poorly understood, despite being essential for development. Folate and cobalamin are B-vitamin cofactors with overlapping roles in transferring various single-carbon units. In mammals, one or both is needed for nucleotide synthesis, DNA methylation, amino acid conversions and other reactions. However, there has been little investigation of the response to folate or cobalamin in insects. Here, we manipulated folate intake and potentially cobalamin levels in the fruit fly Drosophila melanogaster with chemically-defined diets, an antibiotic to reduce bacterially-derived vitamins, and the folate-interfering pharmaceutical methotrexate, to see if single-carbon metabolites and DNA synthesis rates would be affected. We found that similar to mammals with low folate intake, fruit fly larvae had significantly slower growth and DNA synthesis rates. But changes to single carbon-metabolites did not mirror that of mammals with abnormal folate or given MTX. Five of the nine metabolites measured were not significantly affected (methionine, serine, glycine, methylglycine, and dimethylglycine) and three (cystathionine, methylgycine, and methylmalonic acid) were only decreased in larvae consuming methotrexate. Metabolites expected to be elevated if flies used cobalamin from microbial symbionts were not affected by dietary sulfaquinoxaline. Our data support the role of folate in nucleotide synthesis in D. melanogaster and that microbial symbionts provide functioning folates. We could not confirm how folate intake affects single carbon pathway metabolites, nor whether Drososphila use microbially-derived cobalamin. Further work should explore which cofactors are used in fruit flies in these important and potentially novel pathways.",
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AU - Harrison, Jon

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