Vitamin B₁₂ Metabolism: A Network of Multi-Protein Mediated Processes

The water-soluble vitamin, vitamin B₁₂, also known as cobalamin, plays a crucial role in cellular metabolism, particularly in DNA synthesis, methylation, and mitochondrial functionality. Its deficiency can lead to hematological and neurological disorders; however, the manifestation of these clinical outcomes is relatively late. It leads to difficulties in the early diagnosis of vitamin B₁₂ deficiency. A prolonged lack of vitamin B₁₂ may have severe consequences including increased morbidity to neurological and cardiovascular diseases. Beyond inadequate dietary intake, vitamin B₁₂ deficiency might be caused by insufficient bioavailability, blood transport disruptions, or impaired cellular uptake and metabolism. Despite nearly 70 years of knowledge since the isolation and characterization of this vitamin, there are still gaps in understanding its metabolic pathways. Thus, this review aims to compile current knowledge about the crucial proteins necessary to efficiently accumulate and process vitamin B₁₂ in humans, presenting these systems as a multi-protein network. The epidemiological consequences, diagnosis, and treatment of vitamin B₁₂ deficiency are also highlighted. We also discuss clinical warnings of vitamin B₁₂ deficiency based on the ongoing test of specific moonlighting proteins engaged in vitamin B₁₂ metabolic pathways.