Date of Award
Open Access Thesis
Medical Doctor (MD)
Dr. Robert Roth
Since the introduction of the hypothesis that abnormal transmethylation of biogenic amines may be associated with mental illness, transmethylation processes have been shown to be important in the production of biologically active amine derivatives. Laduron has shown that dopamine can be N-methylated with an enzyme from rat brain that requires 5-methyltetrahydrofolic acid (5MTHF ) as a methyl donor. This study shows that the methylation reaction which produces epinine from dopamine is greatest with supernatant from homogenized caudate lobe as compared to the cerebellum, hippocampus, cortex, and raphe nucleus: the brains of male rats were dissected and homogenized, the supernatant was assayed for 5MTHF dependent dopamine-N-methyl transferase activity by incubation with dopamine and C14-5MTHF, separation of the catecholamines with alumina columns, counting radioactivity with a scintillation counter, and identification of epinine with Amberlite column chromatography. The medial forebrain bundle (DA containing neurons) and the raphe nucleus (5HT containing neurons) were lesioned. There was no significant change in enzyme activity in the caudate after these lesions. Human caudate tissue was assayed and found to have significant enzyme activity.
Berv, Douglas A., "Regional Distribution of 5-Methyltetrahydrofolate Dependent Dopamine-N-Methyl Transferase in Rat Brain and Its Presence in Human Brain" (1971). Yale Medicine Thesis Digital Library. 485.