Mechanism of Methionine Toxicity and Its Prevention with Methionine Derivatives
Grant-in-Aid for General Scientific Research (C)
|Allocation Type||Single-year Grants|
|Research Institution||Hokkaido University|
KASAI Takanori Hokkaido University, Faculty of Agriculture Associate Professor, 農学部, 助教授 (80001444)
|Project Period (FY)
1990 – 1991
Completed(Fiscal Year 1991)
|Budget Amount *help
¥1,900,000 (Direct Cost : ¥1,900,000)
Fiscal Year 1991 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1990 : ¥1,300,000 (Direct Cost : ¥1,300,000)
|Keywords||Excess methionine / 2-Keto-4-methylthiobutyric acid / Hypotaurine / Peroxidation of erythrocyte / Hemolytic anemia / Changes in erythrocyte membrane protein / Osmotic fragility of membrane / Cyclo-dimethionine / 脾臓肥大 / αーケトーγーメチルチオ酪酸 / αーヒドロキシーγーメチルチオ酪酸 / オフタルミン酸 / グルタチオン / αーアミノーnー酪酸|
1. Mechanism of Methionine Toxicity
(1)2-Keto-4-methylthiobutyiic acid and 2-hydroxy-4-methylthiobutyric acid, a transamination product of methionine and its derivative, were detected in urine of rats fed an excess methionine diet for the first time, but the amount of the transamination product was very small.
(2)Hypotaurine accumulated in some tissues, especially in muscle, and urine of rats fed methionine excess diet.
(3)Hemolytic anemia developed in excess methionine diet group.
(4)Abnormal erythrocyte, echinocyte, increased significantly in excess methionine diet group.
(5)Erythrocyte membrane of excess methionine diet group was more fragile to osmotic pressure than that fed normal diet.
(6)Plasma peroxide value was very high in excess methionine diet group.
(7)Antioxidant(vitamin E)inhibited the increase of plasma peroxide value and decrease of SOD activity of excess methionine diet group, but could not Prevent the hemolytic anemia, therefore it was unlikely that the peroxidation of erythrocywas the main reason of hemolytic anemia caused by excess methionine intake.
(8)SDS-PAGE of erythrocyte membrane showed the increase of several bands of 35-6OkDa, suggesting that the changes in membrane protein is responsible, at least to some extent, for fragility of erythrocyte membrane caused by excess methionine intake.
(9)The concentration of minerals such as iron and copper in some tissues changed significantly by feeding excess methionine diet.
(10)The symptoms caused by excess methionine intake described above were alleviated by addition of glycine to the diet.
2. Prevention of Methionine Toxicity with Methionine Derivatives with low rate of digestion in and/or absorption from digestive tract.
(1)Rats could not utilize cyclo-dimethionine with cis-peptide bond.
Research Products (9results)