Methylenetetrahydrofolate Dehydrogenase (NAD )
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5,10-Methylenetetrahydrofolate (N5,N10-Methylenetetrahydrofolate; 5,10-CH2-THF) is cofactor in several biochemical reactions. It exists in nature as the diastereoisomer R5,10-methylene-THF. As an intermediate in one-carbon metabolism, 5,10-CH2-THF converts to 5-methyltetrahydrofolate, 5-formyltetrahydrofolate, and methenyltetrahydrofolate. It is substrate for the
enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
methylenetetrahydrofolate reductase (MTHFR), which gives 5-methyltetrahydrofolate. It is mainly produced by the reaction of tetrahydrofolate with serine, catalyzed by the enzyme serine hydroxymethyltransferase.


Selected functions


Formaldehyde equivalent

Methylenetetrahydrofolate is a source of the equivalent of formaldehyde or CH22+ in biosyntheses. Methylenetetrahydrofolate is also an intermediate in the detoxification of
formaldehyde Formaldehyde ( , ) (systematic name methanal) is an organic compound with the chemical formula and structure , more precisely . The compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde. It is stored as ...
.


Pyrimidine biosynthesis

It is the one-carbon donor for thymidylate synthase, for methylation of 2-deoxy-uridine-5-monophosphate (
dUMP Deoxyuridine monophosphate (dUMP), also known as deoxyuridylic acid or deoxyuridylate in its conjugate acid and conjugate base forms, respectively, is a deoxynucleotide. It is an intermediate in the metabolism of deoxyribonucleotides. Biosynthes ...
) to 2-deoxy-thymidine-5-monophosphate ( dTMP). The
coenzyme A cofactor is a non-protein chemical compound or Metal ions in aqueous solution, metallic ion that is required for an enzyme's role as a catalysis, catalyst (a catalyst is a substance that increases the rate of a chemical reaction). Cofactors can ...
is necessary for the
biosynthesis Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme-Catalysis, catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthe ...
of
thymidine Thymidine (nucleoside#List of nucleosides and corresponding nucleobases, symbol dT or dThd), also known as deoxythymidine, deoxyribosylthymine, or thymine deoxyriboside, is a pyrimidine nucleoside, deoxynucleoside. Deoxythymidine is the DNA nuc ...
and is the C1-donor in the reactions catalyzed by TS and thymidylate synthase (FAD).


Biomodulator

R5,10-methylene-THF is a biomodulator that has proven to enhance the desired cytotoxic antitumor effect of Fluorouracil (5-FU) and can bypass the metabolic pathway required by other folates (such as leucovorin) to achieve necessary activation. The active metabolite is being evaluated in clinical trials for patients with colorectal cancer in combination with 5-FU.


See also

* 5,10-Methenyltetrahydrofolate


References

{{DEFAULTSORT:Methylenetetrahydrofolate, 5, 10- Folates Coenzymes