Vitamin B12 deficiency pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Nabeel Ahmed, M.B.B.S

Overview

Dietary Vitamin B12 binds to salivary R factor then the complex arrives at small intestine.^[1]
In duodenum Vitamin B12 is detach from R- factor by pancreatic proteases.
Now free B12 binds to intrinsic factor which is secreted by gastric parietal cell.
The intrinsic factor – B12 complex is absorbed in the ileum.
Absorbed vitamin B12 is use in metabolic pathways which is important for neurologic and hematologic function if vitamin B12 is deficit regardless of the cause many impairments may occur .
Vitamin B12 is a cofactor for the enzyme methionine synthase which convert homocysteine to methionine as a result methyl- THF is converted to THF which is use in synthesis of pyrimidine base of DNA.
In B 12 deficiency homocysteine accumulate which cause megaloblastic anemia and hypersegmented neutrophils.
Vitamin B 12 is a cofactor for enzyme methylmalonyl-COA mutase , which converts methylmalonic-COA to succinyl-COA. In B 12 deficiency methylmalonic acid (MMA ) will accumulate. MMA and elevated level of homocysteine cause damage of myelin as a result subacute combined degeneration of spinal cord ( SCDSC ) occur . This affects dorsal columns, lateral corticospinal tracts and spinocerebellar tract as result loss of proprioception , ataxia , peripheral neuropathy and dementia.