The expression of mitochondrial methylenetetrahydrofolate dehydrogenase-cyclohydrolase supports a role in rapid cell growth.
Deletion of the gene encoding NAD-dependent methylenetetrahydrofolate dehydrogenase-cyclohydrolase (NMDMC) in mice was demonstrated previously to result in failure to establish definitive erythropoiesis in the developing liver. We examined the expression pattern of nmdmc to look for evidence that would support a tissue specific role for this activity. However, whole mount in situ hybridization revealed ubiquitous expression of nmdmc in the tissues of E9.5 and E10.5 embryos suggesting a broader role. Analysis of chimeras demonstrated that nmdmc-/- cells can survive in liver and other tissues of chimeras establishing that the null defect can be rescued by metabolites supplied by surrounding normal cells. Both the expression pattern and metabolite rescue support the proposal that mitochondrial NMDMC provides one-carbon units for purine synthesis during embryogenesis. The elevated expression of NMDMC in tumour cells, but not in surrounding normal cells, is predicted to result in significant differences in folate-mediated support for purine synthesis in the two cell types.
Di Pietro
Erminia
E
Department of Biochemistry, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada H3G 1Y6.
Wang
Xiao-Ling
XL
MacKenzie
Robert E
RE
D000619:Aminohydrolases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002455:Cell Division / Q000502:physiology*; D002678:Chimera; D004622:Embryo, Mammalian / Q000201:enzymology* / Q000502:physiology; D005260:Female; D017403:In Situ Hybridization; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000201:enzymology*; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D011687:Purines / Q000378:metabolism; D014018:Tissue Distribution
D009097:Multienzyme Complexes; D011687:Purines; C055342:methylene tetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP); D000619:Aminohydrolases