Nitrous oxide causes a functional vitamin B12 deficiency by what mechanism?
Irreversible oxidation of the central cobalt ion from its monovalent to divalent state, rendering B12 inactive. Methylcobalamin and adenosylcobalamin, the activated forms of Vitamin B12, are necessary cofactors for two essential enzymes involved in the preservation of myelin: Homocysteine methyltransferase converts homocysteine to methionine. Methionine is the precursor for S-adenosyl methionine, which is required to maintain the neuron sheath. Methylmalonyl-CoA mutase converts methylmalonyl-CoA to succinyl-CoA. This step is necessary for myelin synthesis. In the setting of chronic nitrous oxide abuse subacute combined spinal cord degeneration (SCD) can occur as a result of this functional vitamin B12 deficiency, which manifests clinically as lower extremity weakness, paresthesias and gait abnormalities.
Courtney Temple & B. Zane Horowitz (2022) Nitrous oxide abuse induced subacute combined degeneration despite patient initiated B12 supplementation, Clinical Toxicology, 60:7, 872-875, DOI: 10.1080/15563650.2022.2046772