Nitrous oxide irreversibly oxidizes the cobalt atom of vitaminB12, thereby inhibiting the activity of the cobalamin-dependentenzyme methionine synthase (or 5-methyltetrahydrofolatehomocysteineS-methyltransferase; Enzyme Commission code EC 2.1.1.13). Methioninesynthase catalyzes the remethylation of 5-methyltetrahydrofolateand homocysteine to tetrahydrofolate and methionine (Figure 1).Methionine, by way of its activated form, S-adenosylmethionine,is the principal substrate for methylation in many biochemicalreactions, including assembly of the myelin sheath, methyl substitutionsin neurotransmitters, and DNA synthesis in rapidly proliferatingtissues.1
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Figure 1. The Folate and Homocysteine Metabolic Cycles and the Enzymatic Site of Nitrous Oxide Toxicity.
From the Departments of Anesthesiology (R.R.S., K.H.) and Medical Genetics (R.L.), University of Wisconsin Medical School, Madison; and the Departments of Human Genetics, Medicine, Pediatrics, and Biology, McGill University, Montreal (D.S.R.).
Address reprint requests to Dr. Hogan at the Department of Anesthesiology, B6/319 Clinical Sciences Center, 600 Highland Ave., Madison, WI 53792, or at khogan@facstaff.wisc.edu.
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