5-Methyltetrahydrofolate
Encyclopedia
Levomefolic acid or metafolin (5-methyltetrahydrofolic acid) is the natural, active form of folic acid
used at the cellular level for DNA
reproduction, the cysteine
cycle and the regulation of homocysteine
among other functions. The un-methylated form, folic acid (vitamin B9), is a synthetic form of folate found in nutritional supplements. Synthetic folic acid is metabolized in the body into levomefolic acid. Approximately 10% of the general population (homozygous TT) lack the enzymes needed to receive any benefit from folic acid. Another 40% of the population (heterozygous CT) appear to convert only a limited amount of folic acid into levomefolic acid. They cannot fully process supplemental folic acid at RDA or higher dose levels. The remaining population do not have a known MTHFR polymorphism and can therefore metabolize folic acid more efficiently.
It is synthesized in the absorptive cells of the small intestine from polyglutamylated dietary folate. It is a methylated derivate of tetrahydrofolate (THF, H4F). Levomefolic acid is generated by methylenetetrahydrofolate reductase
(MTHFR) from 5,10-methylenetetrahydrofolate
(5,10-CH2-THF, MTHF) and used to recycle homocysteine
back to methionine
by 5-methyltetrahydrofolate-homocysteine methyltransferase
(MTR) also known as methionine synthase (MS).
Levomefolic acid has been proposed for treatment of cardiovascular disease and advanced cancers such as breast and colorectal cancer
s. It bypasses several metabolic steps in the body and better binds thymidylate synthase
with fDump, a metabolite of the drug fluorouracil
.
Folic acid
Folic acid and folate , as well as pteroyl-L-glutamic acid, pteroyl-L-glutamate, and pteroylmonoglutamic acid are forms of the water-soluble vitamin B9...
used at the cellular level for DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
reproduction, the cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
cycle and the regulation of homocysteine
Homocysteine
Homocysteine is a non-protein amino acid with the formula HSCH2CH2CHCO2H. It is a homologue of the amino acid cysteine, differing by an additional methylene group. It is biosynthesized from methionine by the removal of its terminal Cε methyl group...
among other functions. The un-methylated form, folic acid (vitamin B9), is a synthetic form of folate found in nutritional supplements. Synthetic folic acid is metabolized in the body into levomefolic acid. Approximately 10% of the general population (homozygous TT) lack the enzymes needed to receive any benefit from folic acid. Another 40% of the population (heterozygous CT) appear to convert only a limited amount of folic acid into levomefolic acid. They cannot fully process supplemental folic acid at RDA or higher dose levels. The remaining population do not have a known MTHFR polymorphism and can therefore metabolize folic acid more efficiently.
It is synthesized in the absorptive cells of the small intestine from polyglutamylated dietary folate. It is a methylated derivate of tetrahydrofolate (THF, H4F). Levomefolic acid is generated by methylenetetrahydrofolate reductase
Methylenetetrahydrofolate reductase
Methylenetetrahydrofolate reductase is an enzyme that in humans is encoded by the MTHFR gene. Methylenetetrahydrofolate reductase catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine...
(MTHFR) from 5,10-methylenetetrahydrofolate
5,10-Methylenetetrahydrofolate
5,10-Methylenetetrahydrofolate is the substrate used by the enzyme methylenetetrahydrofolate reductase to generate 5-methyltetrahydrofolate ....
(5,10-CH2-THF, MTHF) and used to recycle homocysteine
Homocysteine
Homocysteine is a non-protein amino acid with the formula HSCH2CH2CHCO2H. It is a homologue of the amino acid cysteine, differing by an additional methylene group. It is biosynthesized from methionine by the removal of its terminal Cε methyl group...
back to methionine
Methionine
Methionine is an α-amino acid with the chemical formula HO2CCHCH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein...
by 5-methyltetrahydrofolate-homocysteine methyltransferase
5-methyltetrahydrofolate-homocysteine methyltransferase
Methionine synthase also known as MS, MeSe, MetH is an enzyme that in humans is encoded by the MTR gene . This enzyme is responsible for the regeneration of methionine from homocysteine...
(MTR) also known as methionine synthase (MS).
Levomefolic acid has been proposed for treatment of cardiovascular disease and advanced cancers such as breast and colorectal cancer
Colorectal cancer
Colorectal cancer, commonly known as bowel cancer, is a cancer caused by uncontrolled cell growth , in the colon, rectum, or vermiform appendix. Colorectal cancer is clinically distinct from anal cancer, which affects the anus....
s. It bypasses several metabolic steps in the body and better binds thymidylate synthase
Thymidylate synthase
Thymidylate synthetase is the enzyme used to generate thymidine monophosphate , which is subsequently phosphorylated to thymidine triphosphate for use in DNA synthesis and repair....
with fDump, a metabolite of the drug fluorouracil
Fluorouracil
Fluorouracil is a drug that is a pyrimidine analog which is used in the treatment of cancer. It is a suicide inhibitor and works through irreversible inhibition of thymidylate synthase. It belongs to the family of drugs called antimetabolites...
.
Commercial use
Commercial use of levomefolic acid in pharmaceutical products began in Europe in the early part of this decade and have now appeared in the U.S. This approach to folate supplementation has potential to impact prenatal care, homocysteine management, and the treatment of depression, dementia and cardiovascular concerns.- Prenatal care: low folate status has been linked to neural tube defects, recurrent pregnancy loss, low birth weight and a variety of age-related high risk complications of pregnancy.
- Homocysteine management: elevated homocysteine is frequently linked to the presence of the MTHFR polymorphismPolymorphism (biology)Polymorphism in biology occurs when two or more clearly different phenotypes exist in the same population of a species — in other words, the occurrence of more than one form or morph...
.
- Depression: folate status has been linked to the performance of SSRI drugs. Many patients have required folate supplementation in order to adequately respond to standard treatment protocol.
- Dementia: folate status has been linked to the efficacy of neural transmitters and cognitive performance. Only active, levomefolic acid can cross the blood brain barrier.
- Diabetic neuropathy: folate status has been shown to have a substantial impact upon wound care.
Brands
Oral doses of levomefolic acid have been developed in Germany and are marketed under the brand name Metafolin.- CerefolinCerefolinCerefolin is a prescription medication made by Pamlab that contains 5.6 mg of folic acid as L-methylfolate, 2 mg of vitamin B12 as methylcobalamin and 600 mg of N-acetylcysteine . It is approved by the U.S. Food and Drug Administration for the treatment or prevention of vitamin...
NAC (5.6 mg) – Nutritional requirements of individuals under a physician's treatment for neurovascular oxidative stress or hyperhomocysteinemia, with particular emphasis for those individuals diagnosed with or at risk for mild to moderate cognitive impairment, vascular dementia, Alzheimer's diseaseAlzheimer's diseaseAlzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
or recurrent or ischemic.
- Deplin (7.5 mg or 15 mg) – Dietary management of suboptimal folate levels in depressed patients.
- MetanxMetanxMetanx is a prescription medication made by Pamlab that contains L-methylfolate , methylcobalamin and pyridoxal 5'-phosphate . It is a vitamin B supplement....
(2.8 mg) – Dietary management of endothelial dysfunctionEndothelial dysfunctionEndothelial dysfunction is a systemic pathological state of the endothelium and can be broadly defined as an imbalance between vasodilating and vasoconstricting substances produced by the endothelium...
in patients with diabetic peripheral neuropathy.
- Néevo and NeevoDHA (1 mg) – Dietary management of those women under a physician's treatment for vitamin deficiency throughout pregnancyPregnancyPregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
, postnatal and the lactating periods. Néevo is specifically indicated for: patients with high risk pregnancies, older OB patients, and patients unable to fully metabolize folic acidFolic acidFolic acid and folate , as well as pteroyl-L-glutamic acid, pteroyl-L-glutamate, and pteroylmonoglutamic acid are forms of the water-soluble vitamin B9...
.
- Zervalx (1 mg) – Dietary management of the following patient conditions: preconception hyperhomocysteinemia; intermediate to higher-risk pregnancies that require an increased dietary folate intake; hemolyticHemolytic anemiaHemolytic anemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells , either in the blood vessels or elsewhere in the human body . It has numerous possible causes, ranging from relatively harmless to life-threatening...
, megaloblasticMegaloblastic anemiaMegaloblastic anemia is an anemia that results from inhibition of DNA synthesis in red blood cell production. When DNA synthesis is impaired, the cell cycle cannot progress from the G2 growth stage to the mitosis stage...
or sickle cell anemia complicated by folate deficiency; and methotrexateMethotrexateMethotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
induced plasma hyperhomocysteinemia.
See also
- 5-Methyltetrahydrofolate-homocysteine methyltransferase5-methyltetrahydrofolate-homocysteine methyltransferaseMethionine synthase also known as MS, MeSe, MetH is an enzyme that in humans is encoded by the MTR gene . This enzyme is responsible for the regeneration of methionine from homocysteine...
(MTR) - S-Adenosylmethionine (SAMe)
- Methylenetetrahydrofolate reductaseMethylenetetrahydrofolate reductaseMethylenetetrahydrofolate reductase is an enzyme that in humans is encoded by the MTHFR gene. Methylenetetrahydrofolate reductase catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine...
(MTHFR) - 5,10-Methylenetetrahydrofolate5,10-Methylenetetrahydrofolate5,10-Methylenetetrahydrofolate is the substrate used by the enzyme methylenetetrahydrofolate reductase to generate 5-methyltetrahydrofolate ....
(5,10-CH2-THF, MTHF)