Subject methylcobalamin

Diabetic neuropathy Oral administration of methylcobalamin (500 meg three times daily for four months) resulted in subjective improvement in burning sensation, numbness, loss of sensation and muscle cramps. 

Interaction with Adenosylcobalamin. It has been considered generally that adenosylcobalamin or its analogs binds to the apoprotein of diol dehydrase or other adenosylcobalamin-dependent enzymes almost irreversibly (4). However, we found that the holo-enzyme of diol dehydrase was resolved completely into intact apoen-zyme and adenosylcobalamin when subjected to gel filtration on a Sephadex G-25 column in the absence of K+ (9, 10). Among the inactive complexes of diol dehydrase with irreversible cobalamin inhibitors, those with cyanocobalamin and methylcobalamin also were resolved upon gel filtration on Sephadex G-25 in the absence of both K+ and substrate, yielding the apoenzyme, which was reconstitutable into the active holoenzyme (II). The enzyme-hydroxocobalamin complex, however, was not resolvable under the same conditions. The enzyme-cobalamin complexes were not resolved at all by gel filtration in the presence of both K+ and substrate. When gel filtration of the holoenzyme was carried out in the presence of K+ only, the holoen-... 

Our laboratory was the first to demonstrate the ability of thimerosal to potently inhibit methionine synthase activity in cultured human neuronal cells (Waly et al., 2004). Subsequent research has shown that inhibition results from a reduction in GSH levels and impaired methylcobalamin synthesis, under conditions where methionine synthase activity is absolutely dependent upon methylcobalamin (M. Waly, unpublished observation). The fact that autistic subjects exhibit lower GSH levels and lower methionine synthase activity lends credence to the mercury... 

The ratio of methylcobalamin to total vitamin derivatives of extractable B12 has been determined in liver from mice who were subjected to different types of injury (mechanical trauma, bums, and ionizing radiation) inflicted separately or in various combinations. A decrease in methylcobalamin was observed paralleling the severity of the damage. There may thus be a decreased synthesis of methycobalamin or an increased catabolism or leakage from the liver—or combination of these causes. The method used did not determine the nonextractable cobalamin, so that a disappearance into a nonextractable form could have been the cause (L9). 

With the refined chromatographic techniques now available for the identification of plasma cobalamins, it has been shown that two-thirds of normal subjects do not have any cyanocobalamin in plasma, and the remainder have only traces, most of the vitamin B12 being in the forms of hydroxocobdamin, methylcobalamin and 5 -deoxyadenosyl i2 ( co-enzyme B12 ). The low cyanocobalamin levels may reflect equilibrating mechanisms which prevent the toted conversion of vitamin B12 to cyanocobalamin which would be expected from the exposure to large eimounts of cyanide by tobacco smokers [56]. 

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