methylenetetrahydrofolate dehydrogenase (NADP )
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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 In stereochemistry, diastereomers (sometimes called diastereoisomers) are a type of stereoisomer. Diastereomers are defined as non-mirror image, non-identical stereoisomers. Hence, they occur when two or more stereoisomers of a compound have dif ...
R5,10-methylene-THF. As an intermediate in one-carbon metabolism, 5,10-CH2-THF interconverts to 5-methyltetrahydrofolate, 5-formyltetrahydrofolate, and methenyltetrahydrofolate. It is substrate for the
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
methylenetetrahydrofolate reductase Methylenetetrahydrofolatereductase (MTHFR) is the rate-limiting enzyme in the methyl cycle, and it is encoded by the ''MTHFR'' gene. Methylenetetrahydrofolate reductase catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrah ...
(MTHFR) It is mainly produced by the reaction of
tetrahydrofolate Tetrahydrofolic acid (THFA), or tetrahydrofolate, is a folic acid derivative. Metabolism Human synthesis Tetrahydrofolic acid is produced from dihydrofolic acid by dihydrofolate reductase. This reaction is inhibited by methotrexate. It is co ...
with serine, catalyzed by the enzyme serine hydroxymethyltransferase.


Selected functions


Formaldehyde detoxification

Methylenetetrahydrofolate is an intermediate in the detoxification of
formaldehyde Formaldehyde ( , ) ( systematic name methanal) is a naturally occurring organic compound with the formula and structure . The pure compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde (refer to section ...
.


Pyrimidine biosynthesis

It is the one-carbon donor for
thymidylate synthase Thymidylate synthase (TS) () is an enzyme that catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP). Thymidine is one of the nucleotides in DNA. With inhibition of TS, an imbalance of deoxynucle ...
, for methylation of 2-deoxy-uridine-5-monophosphate (
dUMP Dump generally refers to a place for disposal of solid waste, a rubbish dump, or landfill. The word has other uses alone or in combination, and may refer to: * Midden, historically a dump for domestic waste * Dump job, a term for criminal disposal ...
) to 2-deoxy-thymidine-5-monophosphate (
dTMP Thymidine monophosphate (TMP), also known as thymidylic acid (conjugate base thymidylate), deoxythymidine monophosphate (dTMP), or deoxythymidylic acid (conjugate base deoxythymidylate), is a nucleotide that is used as a monomer in DNA. It is an ...
). The
coenzyme A cofactor is a non- protein chemical compound or metallic ion that is required for an enzyme's role as a catalyst (a catalyst is a substance that increases the rate of a chemical reaction). Cofactors can be considered "helper molecules" that as ...
is necessary for the
biosynthesis Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecul ...
of
thymidine Thymidine (symbol dT or dThd), also known as deoxythymidine, deoxyribosylthymine, or thymine deoxyriboside, is a pyrimidine deoxynucleoside. Deoxythymidine is the DNA nucleoside T, which pairs with deoxyadenosine (A) in double-stranded DNA. ...
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 Fluorouracil (5-FU), sold under the brand name Adrucil among others, is a cytotoxic chemotherapy medication used to treat cancer. By intravenous injection it is used for treatment of colorectal cancer, oesophageal cancer, stomach cancer, panc ...
(5-FU) and can bypass the metabolic pathway required by other folates (such as
leucovorin Folinic acid, also known as leucovorin, is a medication used to decrease the toxic effects of methotrexate and pyrimethamine. It is also used in combination with 5-fluorouracil to treat colorectal cancer and pancreatic cancer, may be used to tr ...
) 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