Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of vitamin B12 (B12) deficiency on the levels of S-adenosylmethionine (SAM) in tissues and the activities of hepatic methionine synthase, methionine adenosyltransferase and glycine N-methyltransferase were investigated. The striking depression of methionine synthase activity was observed in all rats fed the B12-deficient diets with or without methionine supplementation for 150 days. The SAM level in liver was decreased by B12 deficiency. However, brain SAM level was not affected. The activities of hepatic methionine adenosyltransferase isozymes, alpha-form and beta-form, were decreased by B12 deficiency. Hepatic glycine N-methyltransferase activity in rats fed the low methionine-B12-deficient diet showed a tendency to lower, although the change the activity was not statistically significant, compared with B12-supplemented rats. It is proposed that the fall in the activity of hepatic methionine adenosyltransferase may be one of the causes of the decreased hepatic SAM level in B12-deficient rats.
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PMID:Effect of vitamin B12 deficiency on S-adenosylmethionine metabolism in rats. 273 12

Two independent lines of inquiry have implicated some disturbance of one-carbon cycle metabolism in affective disorders. Folic acid deficiency commonly leads to depression, and S-adenosylmethionine has been reported to have antidepressant properties. Methionine adenosyltransferase has been reported to be underactive in depression and schizophrenia and overactive in mania. This study reports the effects on erythrocyte methionine adenosyltransferase (MAT) kinetics (Vmax) of a 2-week treatment in a population of patients housed on a psychiatric research ward. The drug-free schizophrenic patients and depressives had, upon admission, low Vmax values, and the drug-free manic patients had high Vmax values on admission. After 2 weeks of appropriate treatment, the values for all three patient samples showed significant normalization (i.e., the levels rose in schizophrenics and depressives and fell in manics). We have further shown that pretreatment low levels of erythrocyte membrane phosphatidylcholine in depressives and high levels in manics show statistically significant normalization following 2 weeks of pharmacotherapy. The significance of these results is discussed.
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PMID:Abnormalities of one-carbon metabolism in psychiatric disorders: study of methionine adenosyltransferase kinetics and lipid composition of erythrocyte membranes. 379 Jun 25

A search for control mechanisms involving embryonic genes is explored reviewing a variety of subject areas including, a) the methylation status of DNA and the globin gene, b) ethionine and steroid effects on expression of embryonic genes, c) alpha-fetoprotein gene activity induced by carcinogens and in hepatomas. Also taken into account are transcriptional and cytogenetic aspects. Theories of heterochromatin dynamics are developed in connection with certain contributions from chromatin experimental findings, especially regarding the status of methylation. The potential importance to control theory of the inverse correlation between ATP:L-methionine S-adenosyltransferase activity and alpha-fetoprotein synthesis is emphasized. Several generalizations were derived during the study. It appears that the depression mechanisms may act only on genes that have been active in embryonic stages and have become repressed during differentiation. Another idea concerned heterochromatin. Any heterochromatic segment of DNA may represent at its associated ends a certain amount of euchromatin that would be in a quasi-heterochromatic state. Such pseudoheterochromatin is hypothesized to be induced by the true heterochromatin (eigenheterochromatin).
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PMID:Biochemical formulations of embryonic gene control. 768 50

Mechanisms of selenium methylation and toxicity were investigated in the liver of ICR male mice treated with selenocystine. To elucidate the selenium methylation mechanism, animals received a single oral administration of selenocystine (Se-Cys; 5, 10, 20, 30, 40, or 50 mg/kg). In the liver, both accumulation of total selenium and production of trimethylselenonium (TMSe) as the end-product of methylation were increased by the dose of Se-Cys. A negative correlation was found between production of TMSe and level of S-adenosylmethionine (SAM) as methyl donor. The relationship between Se-Cys toxicity and selenium methylation was determined by giving mice repeated oral administration of Se-Cys (10 or 20 mg/kg) for 10 days. The animals exposed only to the high dose showed a significant rise of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities in plasma. Urinary total selenium increased with Se-Cys dose. TMSe content in urine represented 85% of total selenium at the low dose and 25% at the high dose. The potential of Se-methylation and activity of methionine adenosyltransferase, the enzyme responsible for SAM synthesis, and the level of SAM in the liver were determined. The high dose resulted in inactivation of Se-methylation and decrease in SAM level due to the inhibition of methionine adenosyltransferase activity. To learn whether hepatic toxicity is induced by depressing selenium methylation ability, mice were injected intraperitoneally with periodate-oxidized adenosine (100 mumol/kg), a known potent inhibitor of the SAM-dependent methyltransferase, at 30 min before oral treatment of Se-Cys (10, 20, of 50 mg/kg). Liver toxicity induced by selenocystine was enhanced by inhibition of selenium methylation. These results suggest that TMSe was produced by SAM-dependent methyltransferases, which are identical with those involved in the methylation of inorganic selenium compounds such as selenite, in the liver of mice orally administered Se-Cys. Depression of selenium methylation ability resulting from inactivation of methionine adenosyltransferase and Se-methylation via enzymic reaction was also found in mice following repeated oral administration of a toxic dose of Se-Cys. The excess selenides accumulating during the depression of selenium methylation ability may be involved in the liver toxicity caused by Se-Cys.
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PMID:Mechanisms of selenium methylation and toxicity in mice treated with selenocystine. 901 May 83

S-Adenosylmethionine (SAM) is a key component of sulphur amino acid metabolism in living organisms and is synthesised from methionine and adenosine triphosphate by methionine adenosyltransferase. This molecule serves as the main biological methyl donor due to its active methylthio ether group. Notably, SAM has shown beneficial effects in clinical trials for the treatment of alcoholic liver disease, depression and joint pain. Due to the high potential value of SAM, current research efforts are attempting to develop a more rapid, cost-effective and higher yielding SAM production method than the conventional production system. In this mini-review, we describe the previously reported yeast gene that contributes to SAM accumulation by overexpression, mutation or deletion and summarise the genetic approach for the production of SAM in large industrial quantities.
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PMID:A genetic method to enhance the accumulation of S-adenosylmethionine in yeast. 2807 96