RGD Reference Report - Compartmentalization of Mammalian folate-mediated one-carbon metabolism. - Rat Genome Database

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Compartmentalization of Mammalian folate-mediated one-carbon metabolism.

Authors: Tibbetts, AS  Appling, DR 
Citation: Tibbetts AS and Appling DR, Annu Rev Nutr. 2010 Aug 21;30:57-81. doi: 10.1146/annurev.nutr.012809.104810.
RGD ID: 7242560
Pubmed: PMID:20645850   (View Abstract at PubMed)
DOI: DOI:10.1146/annurev.nutr.012809.104810   (Journal Full-text)

The recognition that mitochondria participate in folate-mediated one-carbon metabolism grew out of pioneering work beginning in the 1950s from the laboratories of D.M. Greenberg, C.G. Mackenzie, and G. Kikuchi. These studies revealed mitochondria as the site of oxidation of one-carbon donors such as serine, glycine, sarcosine, and dimethylglycine. Subsequent work from these laboratories and others demonstrated the participation of folate coenzymes and folate-dependent enzymes in these mitochondrial processes. Biochemical and molecular genetic approaches in the 1980s and 1990s identified many of the enzymes involved and revealed an interdependence of cytoplasmic and mitochondrial one-carbon metabolism. These studies led to the development of a model of eukaryotic one-carbon metabolism that comprises parallel cytosolic and mitochondrial pathways, connected by one-carbon donors such as serine, glycine, and formate. Sequencing of the human and other mammalian genomes has facilitated identification of the enzymes that participate in this intercompartmental one-carbon metabolism, and animal models are beginning to clarify the roles of the cytoplasmic and mitochondrial isozymes of these enzymes. Identifying the mitochondrial transporters for the one-carbon donors and elucidating how flux through these pathways is controlled are two areas ripe for exploration.

Objects Annotated

Genes (Rattus norvegicus)
Amt  (aminomethyltransferase)
Dld  (dihydrolipoamide dehydrogenase)
Dmgdh  (dimethylglycine dehydrogenase)
Gcsh  (glycine cleavage system protein H)
Gldc  (glycine decarboxylase)
Mthfd2  (methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase)
Sardh  (sarcosine dehydrogenase)
Shmt2  (serine hydroxymethyltransferase 2)

Genes (Mus musculus)
Amt  (aminomethyltransferase)
Dld  (dihydrolipoamide dehydrogenase)
Dmgdh  (dimethylglycine dehydrogenase precursor)
Gcsh  (glycine cleavage system protein H (aminomethyl carrier))
Gldc  (glycine decarboxylase)
Mthfd2  (methylenetetrahydrofolate dehydrogenase (NAD+ dependent), methenyltetrahydrofolate cyclohydrolase)
Sardh  (sarcosine dehydrogenase)
Shmt2  (serine hydroxymethyltransferase 2 (mitochondrial))

Genes (Homo sapiens)
AMT  (aminomethyltransferase)
DLD  (dihydrolipoamide dehydrogenase)
DMGDH  (dimethylglycine dehydrogenase)
GCSH  (glycine cleavage system protein H)
GLDC  (glycine decarboxylase)
MTHFD2  (methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase)
SARDH  (sarcosine dehydrogenase)
SHMT2  (serine hydroxymethyltransferase 2)


Additional Information