Aside from its psychopharmacological actions, nitrous oxide has one other
(known) significant metabolic action: it interacts with vitamin B12. This
was first reported in an in vitro study in 1968, but didn't really
receive notice from anaesthesiologists until ten years later (because
medline didn't exist yet
). In 1978, however, Amess et al showed that
24 h of nitrous oxide administration caused interference with DNA
synthesis in humans. Since then, the interaction between nitrous oxide
and B12 has been better characterized.
Basically, B12 is a bound coenzyme of methionine synthase and has a
tetrapyrrole rings with a monovalent cobalt at the center. The cobalt
functions as a methyl carrier in a transmethylation reaction. Nitrous
oxide converts the cobalt from the monovalent form to the bivalent
form. As a result, methionine synthase activity is inhibited. Recovery
is believed to require absorption of new unoxidized B12 (and synthesis
of new apoenzyme).
Humans seem to be far more resistant to complications from this than rodents.
I don't have the energy to go through the various published studies at
this point, so I will quote from Nunn's "Clinical Aspects of the Interaction
Between Nitrous Oxide and Vitamin B12" (1987), _Br. J. Anaesth._ 59: 3-13.
It seems likely that in man, in contrast to the rat, exposure
of less than 30 minutes will not cause any measurable change in
methionine synthase activity. In combination with a wealth of
clinical experience, this suggests that there is no special
hazard for short exposures to nitrous oxide. There is a variable
response to exposures lasting between 30 minutes and 2 h. However,
it now seems likely that exposures of more than 2 h are likely
to cause intereference with hepatic methionine synthase
activity. The paucity of human data makes it more difficult to
say how long an exposure is required to cause significant
intereference with DNA synthesis. It is likely that there will
be considerable individual variation and results obtained in
healthy patients cannot be extrapolated to the patient
who is seriously ill. Nevertheless, it seems likely that,
once methionine synthase activity is inhibited, it will remain
so for days.