Linked Life Data

12949355

Source:http://linkedlifedata.com/resource/pubmed/id/12949355

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2003-9-1
pubmed:abstractText
Methylenetetrahydrofolate reductase (MTHFR) catalyzes the reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the methyl donor for the synthesis of methionine from homocysteine. A common C677T mutation in the MTHFR gene renders the enzyme approximately 50% less active than the wild-type enzyme as shown in in vitro studies using cell extracts. We developed an immortalized cell culture model to determine whether the lower in vitro activity imparted by the homozygous (T/T) genotype is demonstrated in situ when exposed to adequate and marginal physiologic concentrations of folate and riboflavin. T/T MTHFR activity was compared with that of C/C genotype cell extracts by an in vitro assay and in intact cells by measuring the distribution of folate forms, the accumulation of homocysteine in the medium and the synthesis of methionine from formate and homocysteine. Under adequate nutrient conditions, the in vitro activity of the T/T MTHFR enzyme was approximately half that of the C/C genotype. Similarly, the proportion of 5-methyltetrahydrofolate in cells with the T/T genotype was approximately half that of the cells with wild-type MTHFR. In contrast, homocysteine accumulation in the culture medium was low and not different between genotypes, nor was there a difference in methionine synthetic capacity. Significant differences were observed between genotypes only when the supply of both folate and riboflavin was limited in the medium, which resulted in increased homocysteine accumulation and decreased methionine production in the T/T genotype. These data are consistent with the current understanding of the molecular interaction of the MTHFR mutant with folate substrates and the FAD prosthetic group.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-3166
pubmed:author
pubmed:issnType
Print
pubmed:volume
133
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2716-20
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Combined marginal folate and riboflavin status affect homocysteine methylation in cultured immortalized lymphocytes from persons homozygous for the MTHFR C677T mutation.
pubmed:affiliation
Vitamin Metabolism and Aging Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't