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Contribution of mitochondrial serine and glycine‐derived one‐carbon units to deoxynucleoside synthesis in humans
Author(s) -
Quinlivan Eoin Padraig,
Davis Steven R,
Henderson George N,
Stacpoole Peter W,
Gregory Jesse F
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb80-b
Subject(s) - serine hydroxymethyltransferase , glycine , serine , glycine cleavage system , biochemistry , deoxyadenosine , thymidine , chemistry , purine metabolism , metabolism , microbiology and biotechnology , biology , amino acid , dna , enzyme
BACKGROUND Serine and glycine are major one‐carbon donors. In eukaryotic cells one‐carbon metabolism is compartmentalized; the glycine cleavage enzymes are mitochondrial, while the cytosolic and mitochondrial forms of serine hydroxymethyltransferase (SHMT) are independently transcribed. DESIGN One‐carbon donors ([3‐ 13 C]serine, [2, 3, 3‐d 3 ]serine, or [2‐ 13 C]glycine) were administered in separate infusions to healthy males (n = 5). Monocyte DNA was subsequently isolated for the determination of deoxynucleotide enrichment by LC‐MS/MS. RESULTS Total thymidine and deoxyadenosine enrichment was similar for [3‐ 13 C]serine and [2, 3, 3‐d 3 ]serine [ Table]. M+2 thymidine enrichment (i.e., that deriving from cytosolic SHMT) constituted 23% of [2, 3, 3‐d 3 ]serine derived enrichment. Thymidine enrichment from [2‐ 13 C]glycine was lower than from either labeled serine while deoxyadenosine enrichment from [2‐ 13 C]glycine was overestimated, as [2‐ 13 C]glycine was also directly incorporated into purines.Percentage molar enrichment (mean ± SD) of thymidine (dT) and deoxyadenosine (dA). Values in brackets are molar enrichments expressed as a percentage of total one‐carbon enrichment: {enrichment / (enrichment from [2, 3, 3‐d 3 ]serine + enrichment from [2‐ 13 C]glycine)} CONCLUSION The majority (~84%) of one‐carbon units used for thymidine synthesis are mitochondrial derived. Supported by NIH DK56274 and GCRC grant M01‐RR00082