B12 metabolism
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Vitamin B12 Metabolism: An Overview
Introduction to Vitamin B12 Metabolism
Vitamin B12, also known as cobalamin, is a crucial nutrient for human and animal metabolism. It plays a vital role in DNA synthesis, fatty acid and protein metabolism, and other metabolic pathways essential for cellular integrity1 4. The unique structure of vitamin B12, featuring a corrin ligand, was elucidated through X-ray crystallography in the late 1950s1. This vitamin is primarily sourced from microorganisms, as most life forms, except higher plants, depend on these cobalt corrinoids1.
Role in Enzymatic Reactions and Cellular Metabolism
Vitamin B12 functions as a cofactor in several critical enzymatic reactions. It is involved in the metabolism of anaerobic microorganisms and is essential for the homeostasis of methylmalonic acid and homocysteine1 5. The intracellular conversion of vitamin B12 to its active coenzymes, adenosylcobalamin in mitochondria and methylcobalamin in the cytoplasm, is necessary for these processes5. Adenosylcobalamin is required for the catabolism of certain amino acids, while methylcobalamin is crucial for the remethylation of homocysteine to methionine, a reaction that also involves folate7.
Regulatory Roles in Metabolic Pathways
Recent studies have uncovered additional regulatory roles for vitamin B12 beyond its function as an enzyme cofactor. It has been shown to influence the metabolism of folate, ubiquinone, and methionine, thereby playing a pivotal role in cell growth and the coordination of microbial community metabolism2. This regulatory involvement suggests that vitamin B12 is critical for the stability and function of microbiomes, as only a small fraction of organisms can synthesize it de novo2.
Impact on Liver and Lipid Metabolism
Vitamin B12 also significantly affects liver metabolism. Dietary supplementation of vitamin B12 in laying hens has been shown to alter the concentrations of various metabolites in the liver, impacting pathways such as pyrimidine metabolism, vitamin B6 metabolism, and glycerophospholipid metabolism3. Higher levels of vitamin B12 supplementation increased the concentrations of vitamin B12 in both the liver and egg yolk, demonstrating its influence on lipid, nucleic acid, and amino acid metabolic pathways3.
Association with Metabolic Health
Vitamin B12 deficiency is associated with several metabolic disorders. Lower serum levels of vitamin B12 have been linked to obesity, glucose intolerance, increased lipogenesis, and metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH)4. In children, adolescents, and young adults, lower B12 levels correlate with higher body weight, increased adiposity, and worse metabolic health outcomes4.
One-Carbon Metabolism and Disease Prevention
Vitamin B12, along with folate and vitamin B6, is integral to one-carbon metabolism, which is crucial for DNA synthesis and methylation processes6 7. This metabolism involves the transfer of carbon units to tetrahydrofolate (THF), which is then used for the synthesis of thymidine and purines, or for the methylation of homocysteine to form methionine6. Disruptions in this pathway can lead to elevated homocysteine levels, a risk factor for cardiovascular diseases, stroke, and neurocognitive disorders6.
Conclusion
Vitamin B12 is indispensable for numerous metabolic processes, including DNA synthesis, fatty acid and protein metabolism, and the regulation of folate, ubiquinone, and methionine metabolism. Its deficiency can lead to significant metabolic derangements and is associated with various health issues, including obesity and liver diseases. Understanding the multifaceted roles of vitamin B12 in metabolism can help in developing strategies for better health management and disease prevention.
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Most relevant research papers on this topic
Vitamin B12: chemistry and biochemistry.
Vitamin B12 is a cobalt-coordinated vitamin essential for human and animal metabolism, with its unique corrin ligand playing a crucial role in various enzymatic reactions.
Highly CitedElucidation of roles for vitamin B12 in regulation of folate, ubiquinone, and methionine metabolism
Vitamin B12 plays a crucial role in regulating microbial folate, ubiquinone, and methionine metabolism, potentially affecting cell growth and community metabolism coordination.
Highly CitedEffects of dietary supplementation of different levels of vitamin B12 on the liver metabolism of laying hens.
Vitamin B12 supplementation at 25 g/kg in laying hens' diets increases egg yolk vitamin B12 concentration and impacts vitamin B6 metabolism, while 100 g/kg increases egg yolk and liver vitamin B12 concentrations and impacts lipid, nucleic acid, and amino acid metabolic pathways.
RCT
Animal Study
Rigorous JournalLow Levels of Serum Total Vitamin B12 Are Associated with Worse Metabolic Phenotype in a Large Population of Children, Adolescents and Young Adults, from Underweight to Severe Obesity
Low vitamin B12 levels are associated with increased body weight, hepatic insulin resistance, and liver dysfunction in children, adolescents, and young adults, from underweight to severe obesity.
Observational StudyVitamin B12 deficiency
Vitamin B12 deficiency can lead to serious clinical consequences, and diagnosis and management require careful consideration of individual factors and dietary habits.
Systematic Review
Very Rigorous JournalHighly CitedFolate, vitamin B12 and vitamin B6 and one carbon metabolism.
Inadequate intake of folic acid, vitamin B12, and B6 may contribute to aging-related diseases like cognitive decline and Alzheimer's disease.
Highly CitedVitamin B12, folate, and the methionine remethylation cycle—biochemistry, pathways, and regulation
Vitamin B12 and folate play crucial roles in cellular metabolism and regulation of methylation-dependent reactions, with recent advances in understanding their regulation.
Highly CitedCombined biotin, folic acid, and vitamin B12 supplementation given during the transition period to dairy cows: Part I. Effects on lactation performance, energy and protein metabolism, and hormones.
Combined biotin, folic acid, and vitamin B12 supplementation during the transition period improves lactation performance, energy and protein metabolism, and hormones in dairy cows.
RCTRigorous JournalVitamin B12 deficiency
Vitamin B12 deficiency affects individuals of all ages, particularly the elderly, and is caused by inadequate intake, bioavailability, or malabsorption, with management relying on B12 supplementation.
Highly CitedA Missing Link to Vitamin B12 Metabolism
CLYBL gene variants cause reduced vitamin B12 levels in healthy individuals, but its role in B12 metabolism and itaconate production is crucial for maintaining immune function.
Very Rigorous Journal