Studies on the Metabolism of D-and L-Isomers of 3,4-Dihydroxyphenylalanine (DOPA). VI. Metabolism of D-DOPA in Rat Kidney
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概要
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The metabolism of the D-isomer of 3,4-dihydroxyphenylalanine (D-DOPA) in rat kidney was investigated. After incubation of 9.05×10^<-3>м D-DOPA with rat kidney homogenate, 3,4-dihydroxyphenyruvate (DHPP) was detected as the main metabolite, whereas at a lower concentration of D-DOPA (5.22×10^<-4>м), dopamine was the dominant product. It was shown in vitro that D-DOPA is changed to L-DOPA through two steps and decarboxylated immediately to dopamine in rat kidney. The first step is an oxidative deamination of D-DOPA to DHPP by D-amino acid oxidase. This step was inhibited by D-alanine and benzoic acid wherein these substances act as a substrate and inhibitor, respectively. L-Alanine had almost no effect. The K_m value of D-DOPA for purified hog kidney D-amino acid oxidase was 24 mм. The second step is conversion of DHPP to L-DOPA by transaminase. This step was accelerated by aspartate, glutamate, tyrosine, tryptophan and phenylalanine. The latter two were particularly effective as amino donor. L-DOPA was identified by thin-layer chromatography, paper electrophoresis and reverse isotope dilution method. The transaminase activity was observed both in the 9000 g supernatant and precipitate fractions from rat kidney. The rat kidney slice had greater activity than the liver slice in metabolizing D-DOPA to dopamine. This difference is attributable to the content of D-amino acid oxidase in these organs and may give an explanation of the fact that D-DOPA is metabolized in vivo almost exclusively in the kidney.
- 公益社団法人日本薬学会の論文
- 1974-08-25
著者
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進藤 英世
Central Research Laboratories, Sankyo Co., Ltd.
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進藤 英世
Central Research Laboratories Sankyo Co. Ltd.
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前田 満和
National Cancer Center Research Institute
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前田 満和
Central Research Laboratories, Sankyo Co., Ltd.
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進藤 英世
Central Research Labolatories, Sankyo Go., Ltd.
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