Brain methylation and epileptogenesis: the case of methionine sulfoximine.
A brief review of the neurochemical effects of the convulsant agent L-methionine-dl-sulfoximine (MSO) on cerebral methylation reactions is presented. Our findings point to the involvement of a number of endogenous methyl acceptor molecules, including histamine, membrane phospholipids, and membrane proteins, in the mediation of the convulsant effect. Our findings also associate the inhibition of methylations by high levels of S-adenosyl-L-homocysteine in brain with protection against MSO-induced seizures. We propose that MSO acts by eliciting the acceleration of a regulatory methylation-demethylation sequence at key molecular sites, including the benzodiazepine receptor complex, which creates an imbalance in this sequence's normal mediation of convulsant-anticonvulsant mechanisms.
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects; D004827:Epilepsy / Q000139:chemically induced*; D006632:Histamine / Q000378:metabolism; D006710:Homocysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D008715:Methionine / Q000378:metabolism; D008717:Methionine Sulfoximine / Q000633:toxicity*; D008745:Methylation; D008761:Methylhistamines / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism
D008761:Methylhistamines; D009419:Nerve Tissue Proteins; D006710:Homocysteine; D008717:Methionine Sulfoximine; D012436:S-Adenosylmethionine; D006632:Histamine; D012435:S-Adenosylhomocysteine; D008715:Methionine; C007957:homocysteine thiolactone; D000241:Adenosine