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What is the coenzyme form of folic acid?

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3 min read

Over 90% of folate in human plasma circulates as 5-methyltetrahydrofolate (5-MTHF), which is the primary active form of folate in the body. This critical B vitamin, known as folic acid in its synthetic form, must be converted into its coenzyme form to perform essential functions such as DNA synthesis and repair.

Quick Summary

The coenzyme form of folic acid is tetrahydrofolate (THF), which is further processed into various active derivatives like 5-MTHF for metabolic processes. The synthetic form, folic acid, requires conversion by enzymes like DHFR to become biologically usable by the body's cells. Differences exist in how natural folate, folic acid, and 5-MTHF are absorbed and utilized.

Key Points

  • Tetrahydrofolate (THF) is the Coenzyme: The biologically active coenzyme form derived from folic acid is tetrahydrofolate (THF).

  • Conversion is Required: Folic acid is a synthetic, inactive form that must be converted by the body, primarily in the liver, into THF to be used.

  • 5-MTHF is the Circulating Form: The dominant form of folate in the bloodstream is 5-methyltetrahydrofolate (5-MTHF), a derivative of THF.

  • MTHFR Gene Impacts Conversion: A common genetic variant in the MTHFR gene can impair the body's ability to convert folic acid into its active coenzyme forms efficiently.

  • THF Aids Metabolism: The active forms of folate, particularly THF, are crucial for vital metabolic processes, including DNA synthesis, amino acid metabolism, and cell growth.

  • Homocysteine Regulation: The conversion of homocysteine to methionine, a process requiring folate, is essential for regulating homocysteine levels, which affects cardiovascular health.

In This Article

Understanding Folic Acid and its Active Forms

Folic acid is the synthetic, oxidized form of vitamin B9, commonly used in supplements and fortified foods due to its high stability and bioavailability. However, it is not biologically active in this state. For the body to utilize it, a multi-step enzymatic process must convert it into its active coenzyme forms, collectively known as folates. The entire pathway is crucial for one-carbon metabolism, supporting DNA synthesis, amino acid metabolism, and methylation reactions.

The primary coenzyme form of folic acid is tetrahydrofolate (THF). Once absorbed and reduced in the liver, folic acid becomes dihydrofolate (DHF) and then THF via the enzyme dihydrofolate reductase (DHFR). From there, THF can be converted into several derivatives to facilitate various metabolic reactions.

The Folate Conversion Pathway

  1. Folic Acid Intake: Synthetic folic acid is ingested, primarily from supplements and fortified grains.
  2. Conversion to THF: The liver uses DHFR to reduce folic acid first to DHF, then to THF.
  3. One-Carbon Unit Carrier: As THF, the molecule becomes a versatile carrier for one-carbon units (e.g., methyl, methylene) acquired from amino acids like serine.
  4. Formation of 5-MTHF: The enzyme methylenetetrahydrofolate reductase (MTHFR) converts 5,10-methylene-THF into 5-methyl-THF (5-MTHF).
  5. Circulating Form: 5-MTHF is the most abundant and active form of folate found circulating in the bloodstream and is ready for cellular uptake.

The Role of Tetrahydrofolate (THF) in Metabolism

As a coenzyme, THF and its derivatives are fundamental to numerous biological processes. Their core function is to transfer one-carbon units, which are vital for several pathways:

  • Nucleic Acid Synthesis: THF derivatives donate one-carbon units required for the synthesis of purines and the pyrimidine thymidylate, which are essential components of DNA. This is critical for rapid cell division and growth.
  • Amino Acid Metabolism: THF assists in the interconversion of amino acids, such as converting homocysteine into methionine. This link to the methionine cycle is crucial for methylation reactions throughout the body.
  • Homocysteine Regulation: By recycling homocysteine back to methionine, adequate folate levels help prevent the buildup of homocysteine, which is linked to an increased risk of cardiovascular disease.

The Genetic Factor: MTHFR Polymorphism

A significant portion of the population carries a genetic variation, or polymorphism, in the MTHFR gene. This variant can reduce the efficiency of the MTHFR enzyme, impairing the body's ability to convert 5,10-methylene-THF into the active 5-MTHF. For these individuals, supplementation with pre-converted 5-MTHF (L-methylfolate) is more effective than standard folic acid, as it bypasses the enzymatic step that their body struggles to perform.

Folic Acid vs. L-Methylfolate: A Comparison

Feature Folic Acid (Synthetic) L-Methylfolate (Active Coenzyme)
Form Oxidized synthetic compound Reduced and active form of folate
Metabolism Requires multiple enzymatic steps, including DHFR and MTHFR, for conversion Ready for immediate use by the body, bypassing the conversion process
Absorption Highly stable and easily absorbed, but the conversion rate can be limited Highly bioavailable and ensures more folate is readily available
MTHFR Polymorphism Individuals with this genetic variation may have trouble converting folic acid efficiently Ideal for individuals with MTHFR polymorphism as it requires no conversion
Unmetabolized Folic Acid (UMFA) High doses can lead to unmetabolized folic acid in the bloodstream Does not lead to the accumulation of UMFA
Cost Generally more affordable than L-methylfolate Can be more expensive due to its pre-activated form

Conclusion

In summary, while folic acid is a synthetic compound widely used for fortification and supplementation, the true biological work is carried out by its coenzyme form, tetrahydrofolate (THF), and its derivatives, particularly 5-methyltetrahydrofolate (5-MTHF). This conversion process is essential for vital metabolic functions, including DNA synthesis and amino acid regulation. Recognizing the distinction between the synthetic and active forms is crucial for understanding how folate works in the body and for making informed decisions about supplementation, especially for individuals with genetic variations like MTHFR polymorphism. For those seeking a direct and highly bioavailable form of this essential nutrient, L-methylfolate is a superior option that bypasses the body's conversion steps entirely.

References

Frequently Asked Questions

Folate is the general term for naturally occurring forms of vitamin B9, which are found in foods. Folic acid is the synthetic, oxidized form of folate used in supplements and fortified foods, which is not biologically active until converted by the body.

The body converts folic acid into its active coenzyme form, tetrahydrofolate (THF), via a two-step reduction process carried out by the enzyme dihydrofolate reductase (DHFR).

5-MTHF is the most abundant and active form of folate found in human plasma and the primary version transported into cells. It is a derivative of THF and is ready for use by the body's metabolic pathways.

The conversion is vital because folic acid, in its synthetic form, is inactive. The active coenzyme forms derived from this conversion are essential for DNA synthesis, amino acid metabolism, and other critical functions.

The MTHFR gene polymorphism is a genetic variation that can reduce the efficiency of the MTHFR enzyme. For individuals with this variant, converting folic acid to its active 5-MTHF form is less efficient, making L-methylfolate a more effective supplement.

Yes, L-methylfolate is an active form of folate that can be taken as a supplement. It is particularly beneficial for individuals with MTHFR mutations, as it bypasses the need for the body to convert folic acid.

Folate deficiency inhibits DNA synthesis, which impairs the production of red blood cells. This leads to the formation of abnormally large, immature red blood cells, resulting in megaloblastic anemia.

Related Topics:

#metabolism #nutrients #folic acid #folate #vitamin B9 #5-MTHF #tetrahydrofolate #coenzyme

Medical Disclaimer

This content is for informational purposes only and should not replace professional medical advice.