1993 Fiscal Year Final Research Report Summary
Mechanism of Methylguanidine Formation from Creatol
| Project/Area Number |
04671390
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
医学一般
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| Research Institution | Toyama Medical and Pharmaceutical University |
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Principal Investigator |
YOKOZAWA Takako Toyama Medical and Pharmaceutical University, Research Institute for Wakan-Yaku, Associate Professor, 和漢薬研究所, 助教授 (90019133)
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| Project Period (FY) |
1992 – 1993
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| Keywords | Methylguanidine / Creatol / L-Gulono-gammma-lactone oxidase / Methylguanidine synthase / Creatinine / Magnesium lithospermate B |
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| Research Abstract |
Methylguanidine (MG) is strongly suspected to be one of the toxins which induces uremia. We have previously reported that the precursor of MG in vivo is creatinine (Cr). We also demonstrated in in vivo and in vitro experiments that creatol is an intermediate in the process of MG production from Cr and that the hydroxyl radical is involved in the production of creatol from Cr. On the other hand, in normal rats given creatol intraperitoneally, excretion of MG into the urine was increased markedly in comparison with those given Cr, suggesting that creatol-metabolizing enzymes are also involved in this production system. Therefore, we attempted to purify the enzyme responsible for the conversion of creatol to MG and investigated the mechanism of MG production, using samples of liver and kidney, the organs presumably responsible for MG production. MG-synthesizing enzyme was isolated from rat liver microsomes and identufied as L-gulono-gammma-lactone oxidase (EC 1.1.3.8). In addition, MG-synthesizing enzyme was purified from rat kidney lysosomes and peroxisomes. The enzyme was a flavoprotein with a molecular weight of about 37,000 and oxidized creatol to produce MG.The results suggest that the reaction mechanism of this enzyme is different from that of L-gulono-gammma-lactone oxidase.
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