Metabolic Fate of 3,4-Dihydroxyphenylpyruvic Acid (DHPP) in Rats. I. Specific Transformation of DHPP to L-3,4-Dihydroxy-phenylalanine in Vitro
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概要
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3,4-Dihydroxyphenylpyruvic acid-2-^<14>C (DHPP-2-^<14>C) was prepared from glycine-2-^<14>C and the specific formation of L-3,4-dihydroxyphenylalanine (L-DOPA) from DHPP was shown in vitro. The metabolism of L-DOPA-3-^<14>C was also investigated in vitro for comparison. In rat brain and small intestinal homogenates, L-DOPA was formed gradually as the main metabolite from DHPP-2-^<14>C but dopamine and its metabolites were very slight amount. On the contrary, dopamine was detected dominantly from L-DOPA-3-^<14>C in small intestinal homogenates. In the liver and kidney homogenates, DHPP was metabolized extensively and disappeared immediately with concomitant rapid formation of L-DOPA. Dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) were detected subsequently as the main metabolite. The same extensive metabolism of L-DOPA-3-^<14>C was also shown in the liver homogenates. Formation of L-DOPA from DHPP was identified by thin-layer chromatography and reverse isotope dilution method. L-Phenylalanine, L-tyrosine, L-tryptophan and L-glutamate were revealed to be effective amino donors to DHPP. The aromatic L-amino acids were particularly effective but D-phenylalanine showed little activity. The liberation of ^<14>CO_2 from DHPP-2-^<14>C was also recognized in vitro. The ^<14>CO_2 liberating activity from DHPP-2-^<14>C located in 105000 g supernatant soluble fraction in the liver and kidney wherein the activity in the liver was about 4 fold higher than that in the kidney. The activity was inhibited by sodium azide, sodium diethyldithiocarbamate, p-hydroxyphenylpyruvate and phenylpyruvate but not influenced by SKF 525A, carbon monoxide, EDTA, α, α'-dipyridyl and pyruvate. Methylene blue, dichlorphenolindophenol and ascorbate activated about 2-3 fold.
- 社団法人日本薬学会の論文
- 1977-08-25
著者
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進藤 英世
Central Research Laboratories, Sankyo Co., Ltd.
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前田 敏彦
Central Research Laboratories Sankyo Co. Ltd.
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進藤 英世
Central Research Laboratories Sankyo Co. Ltd.
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進藤 英世
Central Research Labolatories, Sankyo Go., Ltd.
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