Inhibition of vitamin B12 metabolism by OH-cobalamin c-lactam in rat oligodendrocytes in culture: a model for studying neuropathy due to vitamin B12 deficiency.

Vitamin B12 is implicated in methylation processes. Myelin basic protein is methylated on one arginine group. A defect in methylation could produce an unstable protein, leading to neurological disorders. In order to study mye lin basic protein, we have developed the cultures of newborn rat oligodendr ocytes in vitamin B12-depleted medium. As these cells do not grow without s erum, vitamin B12 is always present. We overcame this problem by using OH-c obalamin c-lactam, an antagonist of B12. To ensure that the system was vita min B12 deficient, we measured the concentrations of homocysteine and methy lmalonic acid whose accumulations reflect a vitamin B12 deficiency. Methylm alonic acid was measured by mass spectrometry and homocysteine by HPLC. We obtained a powerful model for studying the influence of B12 deficiency on t he synthesis of myelin compounds. (C) 2000 Elsevier Science Ireland Ltd. Al l rights reserved.