1987 Fiscal Year Final Research Report Summary
An approach to pathology of psychiatric disorders by a research on the methylation of membrane proteins
| Project/Area Number |
60480263
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Psychiatric science
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| Research Institution | Ehime University |
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Principal Investigator |
KAKIMOTO Yasuo Ehime University (professor), 医学部, 教授 (60028305)
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| Project Period (FY) |
1985 – 1987
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| Keywords | Membrane protein / Protein N-methylases / Protein carbodymethylases / Calmodulin / schizophrenia / Mania / Adenosylhomocystein |
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| Research Abstract |
While phosphorylation of proteins has been accepted to play essential roles in the regulation of membrane and enzyme functions, biological significance of protein methylation remains unclear in spite of wide occurrences of protein methylation. Nervous systems are the most active organs for protein methylation. We have previously clarified the occurrence of protein methylase of myelin basic protein, and in the present research we found and purified another methylase specific to calmodulin. The enzyme methylates 115 lysine residue of calmoduline obtained from octopus. These proteins are essential proteins for brain stracture and functions.
The activities of two protein carboxymethylases and substrate activities of membrans of erythrocytes were measured in various psychotic and neurological patients. We found an increase in the substrate activity of erythrocytes of manic patients and schizophrenic patients with positive symptoms, which returns to normal value after recovery of the symptoms.
We studied the effects on protein methylation of neutrotransmittors and drugs which modify the synaptic function using the synaptic ending fraction of the rat brain. S-Adenosylhomocystein is a very strong inhibitor which is formed by the reaction of homocystein with intramambrahe adenosine. Regulatory mechanism of protein methylation at synaptic site was suggested.
The last project was directed to study the occurrence of free methylamino acids in the brain. We isolated three methyllysines and three methyl arginines from the TCA extract of the bovine brain. The methods of determination of the methylamino acids were developed to investigate the dynamic state of protein synthesis and degradation.
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