5,10-methylenetetrahydrofolate

5,10-Methylenetetrahydrofolate is a derivative of tetrahydrofolate, a form of folate (vitamin B9) that plays a crucial role in the one-carbon metabolism pathway. This compound is essential for the synthesis of nucleic acids and the methylation of homocysteine to form methionine.

Structure and Function

5,10-Methylenetetrahydrofolate is a coenzyme that participates in the transfer of one-carbon units. It is formed from tetrahydrofolate by the action of the enzyme serine hydroxymethyltransferase, which catalyzes the reversible conversion of serine and tetrahydrofolate to glycine and 5,10-methylenetetrahydrofolate.

In the folate cycle, 5,10-methylenetetrahydrofolate serves as a substrate for the enzyme methylenetetrahydrofolate reductase (MTHFR), which reduces it to 5-methyltetrahydrofolate. This reaction is crucial for the remethylation of homocysteine to methionine, a process that is vital for maintaining normal levels of homocysteine in the blood and for the synthesis of S-adenosylmethionine, a universal methyl donor.

Biological Importance

The role of 5,10-methylenetetrahydrofolate in the synthesis of thymidylate (dTMP) is critical for DNA replication and repair. It donates a methylene group to deoxyuridine monophosphate (dUMP) to form dTMP, a reaction catalyzed by the enzyme thymidylate synthase. This step is essential for the production of thymidine, one of the four nucleotides used in the synthesis of DNA.

Clinical Significance

Deficiencies in the enzymes involved in the metabolism of 5,10-methylenetetrahydrofolate, such as MTHFR, can lead to elevated levels of homocysteine, a condition known as hyperhomocysteinemia. This condition is associated with an increased risk of cardiovascular disease, neural tube defects, and other health issues.

Genetic polymorphisms in the MTHFR gene, such as the C677T mutation, can affect the enzyme's activity and lead to variations in folate metabolism. Individuals with these polymorphisms may require higher intake of folate to maintain normal metabolic function.

Also see

• Folate metabolism
• Methylenetetrahydrofolate reductase
• Homocysteine
• Thymidylate synthase
• One-carbon metabolism