Vitamin B12

  • Also called cobalamin.
  • Function
    • Cofactor for methionine synthase (transfers CH3 groups as methylcobalamin) and methylmalonyl-CoA mutase. Important for DNA synthesis.
    • Cofactor of leucin aminomutase
  • Deficiency
    • Macrocytic, megaloblastic anemia; hypersegmented PMNs; paresthesias and subacute combined degeneration (degeneration of dorsal columns [position sense, vibration, sensory ataxia], lateral corticospinal tracts [UMN spastic paresis, hyperreflexia, Babinski], and spinocerebellar tracts) due to abnormal myelin. Associated with ↑ serum homocysteine and methylmalonic acid levels, along with 2° folate deficiency.
    • Prolonged deficiency → irreversible nerve damage.
    • Found in animal products.
    • Synthesized only by microorganisms. Very large reserve pool (several years) stored primarily in the liver. Deficiency caused by malabsorption (eg, sprue, enteritis, Diphyllobothrium latum, achlorhydria, bacterial overgrowth, alcohol excess), lack of intrinsic factor (eg, pernicious anemia, gastric bypass surgery), absence of terminal ileum (surgical resection, eg, for Crohn disease), pancreatic insufficiency (pancreatic enzymes normally cleave R factor from B12, allowing B12 to be absorbed) or insufficient intake (eg, veganism).
    • Anti-intrinsic factor antibodies diagnostic for pernicious anemia.
    • Folate supplementation can mask the hematologic symptoms of B12 deficiency, but not the neurologic symptoms. Folate alone can worsen demyelination and cause abnormal myelin synthesis by depleting the concentration of unmethylated cobalamin available for methylmalonyl-CoA processing.
  • Excess
    • May antagonize phenytoin → precipitate seizures

 

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