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Effects of the disruption of transmethylation in the central nervous system: an animal model
Author(s) -
Scott John M.,
Molloy Anne M.,
Kennedy D. Glenn,
Kennedy Seamus,
Weir Donald G.,
Scott John M.
Publication year - 1994
Publication title -
acta neurologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.967
H-Index - 95
eISSN - 1600-0404
pISSN - 0001-6314
DOI - 10.1111/j.1600-0404.1994.tb05406.x
Subject(s) - transmethylation , methionine , methionine synthase , cystathionine beta synthase , homocysteine , methyltransferase , methylation , medicine , endocrinology , vitamin b12 , spinal cord , methylcobalamin , cobalamin , homocystinuria , biology , biochemistry , chemistry , amino acid , neuroscience , gene
‐ Central nervous system (CNS) methyltransferases methylate a wide range of substrates including proteins, lipids, nucleic acids and hormones. In every instance the methyl donor is S‐adenosylmethionine (SAMe) and the demethylated product is S‐adenosylhomocysteine (SAH).Methylation can be disrupted when there is an inadequate supply of methionine synthase (following vitamin B 12 deficiency or folate deficiency), SAMe synthetase (due to ethanol), or SAH hydrolase (for unknown reasons). Material and Methods 5‐week‐old pigs were maintained in an environment of either air or nitrous oxide, which inhibits methionine synthase, and were fed eithera methionine‐unsupplemented or methionineenriched diet. After 3 to 10 weeks, pigs were killed by pentabarbitone injection and the levels of methionine and SAMe in the pigs' brain, spinal cord, plasma, liver, and kidney assessed. Results ‐ Pigs maintained in nitrous oxide displayed a dramatic fall in methionine levels in plasma and brain tissues but maintained relatively normal SAMe levels in these tissues. Brain and spinal cord cystathionine levels were markedly elevated, especially in those animals receiving oral methionine, as in the absence of methionine synthase homocysteine can be metabolized only through the catabolic pathway to cystathionine and cysteine. Conclusion ‐ Disorders such as vitamin B 12 deficiency or folate deficiency inhibit methylation by limiting the availability of SAMe or by elevating levels of the inhibitor SAH. In either case, the disruption of a wide range of methylation reactions can cause clinical sequelae ranging from structural abnormalities such as myelopathy to functional abnormalities such as depression.