What is the cofactor for Vitamin B12 (Cobalamin)?

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From the Guidelines

Vitamin B12 serves as a cofactor for two crucial enzymes in the human body: methionine synthase and methylmalonyl-CoA mutase. These enzymes play essential roles in various biological processes, including mitochondrial metabolism, immune response, DNA integrity, and the synthesis of neurotransmitters 1. The cobalt ion at the core of the vitamin B12 molecule is vital for its biological activity, enabling it to participate in these critical enzymatic reactions.

Key Enzymes and Their Functions

  • Methionine synthase: involved in the conversion of homocysteine to methionine, utilizing vitamin B12 as a cofactor 1.
  • Methylmalonyl-CoA mutase: responsible for converting methylmalonyl-CoA to succinyl-CoA, with vitamin B12 serving as a cofactor 1.

Importance of Vitamin B12

The presence of cobalt in the vitamin B12 molecule is essential for its effective functioning in these enzymatic reactions. Inadequate cobalt can lead to impaired vitamin B12 activity, resulting in health issues such as megaloblastic anemia and neurological problems 1.

Clinical Implications

Understanding the role of vitamin B12 as a cofactor for these enzymes is crucial in clinical practice, as it highlights the importance of maintaining adequate vitamin B12 levels to prevent related health issues 1.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Vitamin B12 is essential to growth, cell reproduction, hematopoiesis, and nucleoprotein and myelin synthesis. The FDA drug label does not answer the question.

From the Research

Cofactor for B12

  • Vitamin B12 (cobalamin) is an essential cofactor for two metabolic pathways 2.
  • The two enzymatic conversions of cobalamin into cofactor forms are via methionine synthase and methylmalonyl-CoA-mutase, resulting in methylcobalamin and adenosylcobalamin 2.
  • Methylcobalamin and adenosylcobalamin are the cofactor forms of vitamin B12 that play a crucial role in various cellular processes, including DNA synthesis, methylation, and mitochondrial metabolism 3.

Metabolic Pathways

  • Vitamin B12 is a cofactor for the enzyme methionine synthase, which is involved in the conversion of homocysteine to methionine 2, 3.
  • Vitamin B12 is also a cofactor for the enzyme methylmalonyl-CoA-mutase, which is involved in the conversion of methylmalonyl-CoA to succinyl-CoA 2, 4.

Importance of Cofactor

  • The cofactor forms of vitamin B12, methylcobalamin and adenosylcobalamin, are essential for maintaining normal cellular function and preventing deficiency-related disorders 2, 3.
  • Deficiency of vitamin B12 can lead to various clinical manifestations, including megaloblastic anemia, neuropsychiatric symptoms, and other health problems 5, 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Vitamin B12 deficiency.

Nature reviews. Disease primers, 2017

Research

Vitamin B12 Deficiency: Recognition and Management.

American family physician, 2017

Research

Pernicious anemia: Pathophysiology and diagnostic difficulties.

Journal of evidence-based medicine, 2021

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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