Abstract

Vitamin B12 (cobalamin) is an essential micronutrient with a pivotal role in DNA synthesis, cellular replication, and maintenance of genomic stability. Its biochemical functions are mediated through two enzymatic reactions that are critical for the integrity of nucleotide biosynthesis and the proper functioning of the methylation cycle. Firstly, Vitamin B12 acts as a cofactor for methionine synthase, an enzyme responsible for the remethylation of homocysteine to methionine. Methionine is subsequently converted to S-adenosylmethionine (SAM), the primary methyl group donor used in the methylation of DNA, RNA, proteins, and lipids. DNA methylation is a key epigenetic mechanism that regulates gene expression, ensuring proper chromatin structure and genomic stability. Disruptions in this pathway due to Vitamin B12 deficiency can lead to aberrant DNA methylation patterns, which are associated with various pathological conditions, including cancer, cardiovascular diseases, and neurodegenerative disorders. Secondly, Vitamin B12 is involved in the conversion of methylmalonyl-CoA to succinyl-CoA via the enzyme methylmalonyl-CoA mutase. This reaction is crucial for the catabolism of odd-chain fatty acids and certain amino acids, and it also plays a role in the synthesis of deoxyribonucleotides, the building blocks of DNA. Impaired function of methylmalonyl-CoA mutase due to Vitamin B12 deficiency results in the accumulation of methylmalonic acid, which can disrupt mitochondrial function and contribute to neurotoxicity. Clinically, Vitamin B12 deficiency manifests in various hematological and neurological symptoms. The most notable is megaloblastic anemia, characterized by the presence of large, immature, and dysfunctional erythrocytes in the bloodstream. This condition arises from impaired DNA synthesis, which leads to ineffective erythropoiesis and the arrest of cell division. Neurological complications, including peripheral neuropathy, cognitive decline, and myelopathy, are also common, resulting from disrupted myelin synthesis and maintenance. In conclusion, Vitamin B12 is indispensable for the maintenance of DNA integrity, efficient cellular replication, and the overall health of the hematological and nervous systems. Adequate levels of this vitamin are crucial to prevent DNA damage, support proper methylation processes, and protect against the long-term consequences of deficiency, including anemia, neurodegeneration, and increased disease susceptibility.