HydroxyB12 Reduces Nitric Oxide

[ddjd]

"One of the most interesting approaches to inhibiting carbon monoxide production is to use vitamin B12, as hydroxocobalamin, as an antidote to nitric oxide, preventing the nitric oxide from stimulating the formation of heme oxygenase."

I'm geussing the methyl b12 form doesn't have this same effect on nitric oxide?

 

[Waynish]

So it would be good for smokers?

 

[Terma]

Martin Pall could probably have answered this question in 2 sentences for you 15 years ago, but I don't know what he's been doing, so here's the only answer I remember reading:
INHIBITION OF NITRIC OXIDE SYNTHASE BY COBALAMINS AND COBINAMIDES*

Cobalamins (Cbl) are important co-factors for methionine synthase and methylmalonyl-coA mutase. Certain corrins also bind nitric oxide (NO), quenching its bioactivity. To determine if corrins would inhibit NO synthase (NOS), we measured their effects on 14-C-L-arginine-to-14-C-L-citrulline conversion by NOS1, NOS2, and NOS3. Hydroxocobalamin (OH-Cbl), cobinamide (Cbi), and dicyanocobinamide (CN2-Cbi) potently inhibited all isoforms, whfile cyanocobalamin, methylcobalamin, and adenosylcobalamin had much less effect. OH-Cbl and CN2-Cbi prevented binding of the oxygen analog carbon monoxide (CO) to the reduced NOS1 and NOS2 heme active site. CN2-Cbi did not react directly with NO or CO. Spectral perturbation analysis showed that CN2-Cbi interacted directly with the purified NOS1 oxygenase domain. NOS inhibition by corrins was rapid and not reversed by dialysis with L-arginine, tetrahydrobiopterin. Molecular modeling indicated that corrins could access the unusually large heme and substrate-binding pocket of NOS. Best fits were obtained in the “base-off” conformation of the lower axial dimethylbenzimidazole ligand. CN2-Cbi inhibited interferon-γ-activated Raw264.7 mouse macrophage NO production. We show for the first time that certain corrins directly inhibit NOS, suggesting that these agents (or their derivatives) may have pharmacological utility. Endogenous cobalamins and cobinamides might play important roles regulating NOS activity in normal and pathological conditions.

 

[ddjd]

Martin Pall could probably have answered this question in 2 sentences for you 15 years ago, but I don't know what he's been doing, so here's the only answer I remember reading:
INHIBITION OF NITRIC OXIDE SYNTHASE BY COBALAMINS AND COBINAMIDES*

Thanks for posting this