What are the co enzymes of vitamin B12? A guide to methylcobalamin and adenosylcobalamin

November 27, 2025 •

4 min read

Vitamin B12 is the most chemically complex of all vitamins and is crucial for numerous bodily functions. The two primary coenzymes of vitamin B12 are methylcobalamin and adenosylcobalamin, which are essential for different metabolic processes. These two active forms are vital for everything from DNA synthesis to energy production and maintaining a healthy nervous system.

Quick Summary

The two active coenzymes of vitamin B12 are methylcobalamin and adenosylcobalamin, which perform distinct yet complementary functions in the body's metabolic pathways. They are essential for processes like DNA synthesis, energy production within mitochondria, and proper neurological function.

Key Points

Methylcobalamin and adenosylcobalamin: These are the two active coenzyme forms of vitamin B12, vital for different enzymatic reactions in the human body.
Methylcobalamin's function: It is a cofactor for methionine synthase, converting homocysteine to methionine and is essential for DNA synthesis and the methylation cycle.
Adenosylcobalamin's function: Primarily active in mitochondria, it is a cofactor for methylmalonyl-CoA mutase, crucial for energy production from fatty acids and amino acids.
Deficiency symptoms: A lack of B12 coenzymes can cause a range of symptoms, including megaloblastic anemia, fatigue, nerve damage (neuropathy), and cognitive issues.
Diagnostic markers: Elevated levels of homocysteine and methylmalonic acid (MMA) can indicate a deficiency in methylcobalamin and adenosylcobalamin, respectively.
Conversion from other forms: The common supplemental form, cyanocobalamin, must be converted by the body into the active methylcobalamin and adenosylcobalamin.
Neurological protection: Adenosylcobalamin is particularly important for the health of the myelin sheath that insulates and protects nerve cells.

The Core Coenzymes: Methylcobalamin and Adenosylcobalamin

Vitamin B12, also known as cobalamin, is not used directly by the body in its inactive form. Instead, it must be converted into its biologically active coenzyme forms to assist enzymes in catalyzing metabolic reactions. These two primary active coenzymes are methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl). Both are essential for life and play distinct, critical roles in human metabolism.

The Role of Methylcobalamin

Methylcobalamin is primarily active in the cytoplasm of cells and plays a vital role in one-carbon metabolism, specifically in the remethylation cycle. Its most well-known function is as a cofactor for the enzyme methionine synthase (or homocysteine methyltransferase). This enzyme catalyzes the conversion of homocysteine into methionine.

Without adequate methylcobalamin, this critical step is impaired, leading to a buildup of homocysteine, an amino acid linked to cardiovascular disease and dementia when elevated. Methionine is then converted into S-adenosylmethionine (SAMe), a universal methyl donor used in numerous methylation reactions, including those affecting DNA and neurotransmitters.

Furthermore, the regeneration of methionine by methionine synthase is crucial for recycling folate. The reaction converts 5-methyl-tetrahydrofolate (the inactive storage form of folate) back into active tetrahydrofolate. A deficiency in methylcobalamin can therefore trap folate in its inactive form, a phenomenon known as the "methyl-folate trap," which impairs DNA synthesis and cell division. This can lead to megaloblastic anemia, a hallmark sign of advanced B12 deficiency.

The Role of Adenosylcobalamin

In contrast to methylcobalamin's cytoplasmic role, adenosylcobalamin is predominantly active within the mitochondria, the powerhouse of the cell. Here, it acts as a cofactor for the enzyme methylmalonyl-CoA mutase.

This enzyme facilitates the conversion of methylmalonyl-CoA to succinyl-CoA, a key intermediate in the citric acid cycle (Krebs cycle) for energy production. This pathway is essential for the metabolism of odd-chain fatty acids and some amino acids. When adenosylcobalamin levels are insufficient, methylmalonyl-CoA accumulates and is converted into methylmalonic acid (MMA). Elevated MMA levels can serve as a diagnostic marker for B12 deficiency and, if left unchecked, can lead to demyelination and severe neurological damage.

Adenosylcobalamin is also a vital component for maintaining the health of the nervous system and the myelin sheath that protects nerve cells. Damage to the myelin sheath due to adenosylcobalamin deficiency can cause a range of neurological symptoms, including tingling sensations, numbness, problems with balance, and cognitive issues.

Distinctions Between the Coenzymes

Comparison of Methylcobalamin and Adenosylcobalamin


Feature	Methylcobalamin (MeCbl)	Adenosylcobalamin (AdoCbl)
Primary Cellular Location	Cytoplasm	Mitochondria
Key Enzymatic Function	Cofactor for methionine synthase	Cofactor for methylmalonyl-CoA mutase
Associated Metabolic Pathway	Remethylation of homocysteine	Conversion of methylmalonyl-CoA to succinyl-CoA
Primary Role	DNA synthesis, homocysteine regulation, methylation cycle	Energy metabolism, fatty acid breakdown, neurological protection
Associated Deficiency Marker	High homocysteine levels	High methylmalonic acid (MMA) levels
Impact on Deficiency Symptoms	Anemia and certain neurological issues	Primarily neurological damage, demyelination, and energy issues

Synthesis from Other B12 Forms

It is important to note that the different forms of vitamin B12 found in foods and supplements, such as cyanocobalamin and hydroxocobalamin, are not themselves active coenzymes. Cyanocobalamin, the most stable and common form used in supplements and fortified foods, must be converted into methylcobalamin and adenosylcobalamin within the body. For this reason, some individuals prefer supplements that contain the active coenzyme forms directly, especially those with certain genetic variations that may affect the conversion process.

Conclusion

In summary, the two essential coenzymes of vitamin B12 are methylcobalamin and adenosylcobalamin, and their functions are critical for maintaining human health. Methylcobalamin's role in the cytoplasm ensures proper DNA synthesis and the metabolism of homocysteine, preventing megaloblastic anemia and supporting brain health. Adenosylcobalamin, in the mitochondria, is key to energy metabolism, the breakdown of fatty acids, and the formation of the nerve-protecting myelin sheath. A deficiency in B12 can disrupt these vital functions, leading to a cascade of physical, neurological, and psychological issues. Ensuring adequate intake of these coenzymes, either through animal-derived foods or supplementation, is paramount, particularly for individuals on vegetarian or vegan diets or those with absorption issues.

How to Supplement for Optimal Levels

For those needing to increase their B12 levels, especially in cases of dietary restriction or malabsorption, several options exist:

Oral Supplements: The most common approach involves taking oral supplements, which can come in various forms, including tablets, capsules, or sublingual melts. While cyanocobalamin is the most stable form, supplements containing methylcobalamin and adenosylcobalamin are also widely available and preferred by some.
Dietary Sources: For those who are not vegan or vegetarian, consuming animal products like meat, fish, eggs, and dairy can help maintain B12 levels. Beef liver, clams, and fortified foods are particularly rich sources.
Fortified Foods: Many cereals, plant-based milks, and nutritional yeasts are fortified with vitamin B12, offering a reliable dietary source for vegans and vegetarians.
Vitamin B12 Injections: For severe deficiencies or absorption disorders like pernicious anemia, intramuscular injections of vitamin B12 (often hydroxocobalamin or cyanocobalamin) are often prescribed to bypass the digestive system entirely.

Consulting a healthcare provider is essential to determine the best strategy for your specific needs, as an unaddressed deficiency can lead to irreversible nerve damage.

PubChem: Adenosylcobalamin

Frequently Asked Questions

Methylcobalamin functions in the cytoplasm for DNA synthesis and homocysteine regulation, while adenosylcobalamin works in the mitochondria for energy production and myelin sheath maintenance. They are both crucial but support different metabolic processes.

Neither is definitively better; rather, they are complementary. Most experts suggest a combination of both methylcobalamin and adenosylcobalamin, especially for those with genetic factors affecting conversion, to ensure comprehensive coverage for all B12-dependent processes.

Yes, both active coenzymes are naturally present in animal-derived foods like meat, eggs, and dairy products. However, individuals on vegan or vegetarian diets, or those with malabsorption issues, will likely need fortified foods or supplements to get sufficient amounts.

Both coenzymes are essential for neurological health. Methylcobalamin aids in producing neurotransmitters and supports overall nerve function, while adenosylcobalamin helps maintain the myelin sheath that protects nerve cells.

Initial symptoms can be gradual and include fatigue, weakness, and pale skin due to megaloblastic anemia. Neurological symptoms such as tingling in the hands and feet and memory problems often appear later, as the deficiency worsens.

Yes, the body converts the synthetic cyanocobalamin into the active coenzymes, methylcobalamin and adenosylcobalamin. However, this conversion process may be inefficient in some individuals, prompting the use of pre-activated forms in supplements.

Vitamin B12, through its coenzyme methylcobalamin, is involved in the metabolic pathway that regenerates active folate. This active folate is a necessary precursor for building blocks of DNA, so a B12 deficiency can disrupt DNA synthesis.