The enzyme MTHFD1L does not directly catalyze the conversion of homocysteine to methionine. Also, there is no current evidence that mutations in the gene for MTHFD1L cause elevated homocysteine levels. The finding that a variant of MTHFD1L is linked to the risk of AD is very interesting, but the mechanism of its effect is likely to be complex. MTHFD1L is the mitochondrial form of an enzyme whose function is to catalyze a reversible transformation of 5,10-methylenetetrahydrofolate to 10-formyl tetrahydrofolate (10-formylTHF). 10-formylTHF serves as a formyl donor for MET-tRNA in mitochondrial protein synthesis, and as a precursor of purines. 10-formylTHF may also be hydrolyzed to formate, which passes out of the mitochondria into the cytoplasm. In the cytoplasm formate enters the one-carbon pool through an ATP-dependent conversion to 10-formylTHF, catalyzed by the trifunctional enzyme MTHFD1—the cytoplasmic form of the enzyme (MacFarlane et al., 2009). So, the most that can be said about a variant of MTHFD1L is that it might well in some way interfere with normal one-carbon...  Read more

The enzyme MTHFD1L does not directly catalyze the conversion of homocysteine to methionine. Also, there is no current evidence that mutations in the gene for MTHFD1L cause elevated homocysteine levels. The finding that a variant of MTHFD1L is linked to the risk of AD is very interesting, but the mechanism of its effect is likely to be complex. MTHFD1L is the mitochondrial form of an enzyme whose function is to catalyze a reversible transformation of 5,10-methylenetetrahydrofolate to 10-formyl tetrahydrofolate (10-formylTHF). 10-formylTHF serves as a formyl donor for MET-tRNA in mitochondrial protein synthesis, and as a precursor of purines. 10-formylTHF may also be hydrolyzed to formate, which passes out of the mitochondria into the cytoplasm. In the cytoplasm formate enters the one-carbon pool through an ATP-dependent conversion to 10-formylTHF, catalyzed by the trifunctional enzyme MTHFD1—the cytoplasmic form of the enzyme (MacFarlane et al., 2009). So, the most that can be said about a variant of MTHFD1L is that it might well in some way interfere with normal one-carbon metabolism, in particular if folate status is compromised. There is much evidence that changes in one-carbon metabolism may be related to AD (Smith, 2008), but without further data we cannot yet directly link the new finding to homocysteine.

References:
MacFarlane, A. J., C. A. Perry, et al. (2009). MTHFD1 is an essential gene in mice and alters biomarkers of impaired one-carbon metabolism. J Biol Chem 284(3): 1533-1539. Abstract

Smith, A. D. (2008). The worldwide challenge of the dementias: A role for B vitamins and homocysteine? Food Nutr Bull 29: S143-172. Abstract

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