MTHFD1L

Monofunctional C1-tetrahydrofolate synthase, mitochondrial also known as formyltetrahydrofolate synthetase, is an is_associated_with::enzyme that in humans is encoded by the MTHFD1L is_associated_with::gene (methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-like).

Function
One-carbon substituted forms of tetrahydrofolate (THF) are involved in the is_associated_with::de novo synthesis of is_associated_with::purines and thymidylate and support cellular is_associated_with::methylation reactions through the regeneration of is_associated_with::methionine from is_associated_with::homocysteine. MTHFD1L is an enzyme involved in THF synthesis in mitochondria.

In contrast to is_associated_with::MTHFD1 that has trifunctional methylenetetrahydrofolate dehydrogenase, is_associated_with::methenyltetrahydrofolate cyclohydrolase, and formyltetrahydrofolate synthetase enzymatic activities, MTHFD1L only has formyltetrahydrofolate synthetase activity.

Clinical significance
Certain variants of the MTHFD1L are associated is_associated_with::neural tube defects.

Model organisms
is_associated_with::Model organisms have been used in the study of MTHFD1L function. A conditional is_associated_with::knockout mouse line, called Mthfd1ltm1a(EUCOMM)Wtsi was generated as part of the is_associated_with::International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.

Male and female animals underwent a standardized is_associated_with::phenotypic screen to determine the effects of deletion. Twenty six tests were carried out on is_associated_with::mutant mice and two significant abnormalities were observed. The is_associated_with::homozygous is_associated_with::mutant embryos identified during gestation had is_associated_with::exencephaly. None survived until is_associated_with::weaning. The remaining tests were carried out on is_associated_with::heterozygous mutant adult mice and no further abnormalities were observed.