| Project/Area Number |
61570123
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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 |
General medical chemistry
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| Research Institution | Osaka University Medical School |
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Principal Investigator |
IMAMURA Ikuo Department of Pharmacology II, Osaka University Medical School, 医学部, 助手 (90176496)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUI Hiroyuki Department of Pharmacology II, Osaka University Medical School, 医学部, 助教授 (90112052)
WADA Hiroshi Department of Pharmacology II, Osaka University Medical School, 医学部, 教授 (30028295)
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1987: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1986: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | N^<<tau>>-(beta)-ribosylhistidine / ADP-ribosylation / NAD^+ GLYCOHYDROLASE / ヒスタミン / 【N^Υ】-β-リボシルヒスチジン / 【NAD^+】グリコヒドロラーゼ |
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| Research Abstract |
We found a movel histidine derivative in the urine of hyper-histidinemic patient and determined its structure as N^<<tau>>-<beta>-D-ribofuranosyl-L-histidine (HisR). In this project the biosynthetic pathway of HisR and its physiological significance were investigated.
NAD^+ glycohydrolase, which transfers ADP-ribose moiety to imidazole group of histidine, and nucleotide pyrophosphatase, which hydrolyses histidine adenine dinucleotide to adenylate and 5'phosphoribosylhistidine, are both membrance bound enzymes and were solubilized by lipase and triton X-100 respectively. They were purified 300 and 200 fold respectively by ion-exchange chromatography and gel-filtration. These two wnzymes and alkaline-phosphatase (as replace of 5'-nucleotidase) could produce ribosylhistidine in vitro.
The translation efficacy of NAD' glycohydrolase was much better when histidine containing peptide in place of histidine itself was used as substrate. But reguretably the investigation of protein substrate of NAD^+ glycohydrolase was not successful.
The urinary excretion of ribosylhistidine were found to increase in middle (11-20 week of gestation) and late (33-40 week of human pregnancy.
Using rats as model animal, it was revealed that the middle increase was occurred by increased histidine utilization and the late one by fetus production of ribosylhistidine, especially in liver.
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