Nitrous oxide-induced B₁₂ deficiency myelopathy: Perspectives on the clinical biochemistry of vitamin B₁₂.
Beginning with a case report of nitrous oxide (N₂O)-induced B₁₂ deficiency myelopathy, this article reviews the clinical biochemistry of vitamin B₁₂, and examines the pathogenetic mechanisms by which B₁₂ deficiency leads to neurologic damage, and how this damage is potentiated by N₂O exposure. The article systematically examines the available experimental data relating to the two main coenzyme mechanisms that are usually suggested in clinical articles, particularly the deficient methylation hypothesis. The article demonstrates that neither of these mechanisms is fully consistent with the available data. The article then presents a novel mechanism based on new data from the neuroimmunology basic science literature which suggests that the pathogenesis of B₁₂ deficiency myelopathy may not be related to its role as a coenzyme, but rather to newly discovered functions of B₁₂ in regulating cytokines and growth factors.
Stanford University, Department of Biology, USA. lhathout@aol.com
Leith
L
Hathout
Suzie
S
El-Saden
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000378:metabolism; D000818:Animals; D003038:Cobamides / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D005492:Folic Acid / Q000378:metabolism; D020234:Gait Ataxia / Q000209:etiology; D006801:Humans; D013287:Illicit Drugs / Q000009:adverse effects*; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008297:Male; D008745:Methylation; D008764:Methylmalonic Acid / Q000097:blood; D008765:Methylmalonyl-CoA Mutase / Q000378:metabolism; D023421:Models, Animal; D008954:Models, Biological; D009609:Nitrous Oxide / Q000009:adverse effects*; D011178:Postgastrectomy Syndromes / Q000378:metabolism; D011712:Pyramidal Tracts / Q000473:pathology; D013116:Spinal Cord / Q000473:pathology; D052879:Subacute Combined Degeneration / Q000139:chemically induced* / Q000175:diagnosis / Q000378:metabolism; D019966:Substance-Related Disorders / Q000150:complications* / Q000378:metabolism; D014805:Vitamin B 12 / Q000737:chemistry / Q000378:metabolism; D055815:Young Adult
D003038:Cobamides; D016207:Cytokines; D013287:Illicit Drugs; D036341:Intercellular Signaling Peptides and Proteins; D008764:Methylmalonic Acid; D005492:Folic Acid; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D008765:Methylmalonyl-CoA Mutase; D009609:Nitrous Oxide; D014805:Vitamin B 12