Clinical aspects of the interaction between nitrous oxide and vitamin B12.

Vitamin BM is a bound coenzyme of methionine synthase and has a tetrapyrrole ring with monovalent cobalt at the centre. The cobalt functions as a methyl carrier in the transmethylation reaction shown in figure 1. In 1968, Banks, Henderson and Pratt reported that nitrous oxide reacted in vitro with vitamin B12, converting the cobalt from the monovalent form (Cob(I)alamin) to the bivalent form (Cob(II)alamin), which can no longer function as a methyl carrier. Their paper, in a journal not perused by many in the biomedical field, remained unnoticed by both haematologists and anaesthetists for 10 years. In a seminal study, Amess and his colleagues (1978) showed that 24 h of administration of nitrous oxide to patients caused interference with deoxyribonucleic acid (DNA) synthesis, and they correctly inferred that nitrous oxide had interfered with the function of vitamin B,,. A few months later, Deacon and her colleagues (1978) showed that nitrous oxide did in fact cause rapid inhibition of the activity of methionine synthase in the rat. Also in the same journal and the same year, Layzer (1978) reported a condition resembling sub-acute combined degeneration of the cord in 15 patients who had been chronically exposed to high concentrations of nitrous oxide. There was thus a parallel with megaloblastic anaemia and a working hypothesis for the agranulocytosis and the teratogenesis which had previously been observed as toxic effects of nitrous oxide.