A Metabolomic Approach For Characterizing Methylenetetrahydrofolate Reductase Mutations And Possible Outcomes For The Treatment of Related Diseases
EMSL Project ID
30415
Abstract
N5,N10-Methylenetetrahydrofolate reductase (MTHFR) is a flavoprotein that catalyzes the conversion of N5,N10-methylenetetrahydrofolate to N5-methyltetrahydrofolate. This reaction is required for the multi-step process that converts homocysteine to methionine. At least 43 mutations have been identified in the MTHFR gene, most causing a single amino acid change in the MTHFR protein resulting in either a non-functioning enzyme or an enzyme with reduced activity. Reduced MTHFR activity leads to hyperhomocysteinemia, a condition where homocysteine builds up in the bloodstream and methionine levels are depleted. For reasons that are poorly understood, hyperhomocysteinemia is associated with increased risk of cardiovascular disease and stroke, cognitive impairment, neural tube defects, and other neurological and psychiatric disorders. Elevated plasma homocysteine is probably not the main cause of these disorders and reduced plasma homocysteine, by itself, is inadequate as an indicator of effective therapies. Our goal is to apply NMR-based metabolomics to identify metabolites (biomarkers) associated with deficiencies in folic acid metabolism, and subsequently, to examine if these enzyme deficiencies play a role in the etiology of related diseases, such as fibromyalgia. Because fibromyalgia is a syndrome and there is no test for its diagnosis, the ability to recognize a correlation between symptoms and metabolism could lead to targeted therapies, thereby reducing healthcare costs for many individuals across the nation.
Project Details
Project type
Large-Scale EMSL Research
Start Date
2008-10-01
End Date
2009-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members