Oxidation of Indole by Cytochrome P450 Enzymes

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• 作者：Elizabeth M. J. Gillam ; Lisa M. Notley ; Hongliang Cai ; James J. De Voss ; and F. Peter Guengerich
• 刊名：Biochemistry
• 出版年：2000
• 出版时间：November 14, 2000
• 年：2000
• 卷：39
• 期：45
• 页码：13817 - 13824
• 全文大小：94K
• 年卷期：v.39,no.45(November 14, 2000)
• ISSN：1520-4995

文摘

Indole is a product of tryptophan catabolism by gut bacteria and is absorbed into the body insubstantial amounts. The compound is known to be oxidized to indoxyl and excreted in urine as indoxyl(3-hydroxyindole) sulfate. Further oxidation and dimerization of indoxyl leads to the formation of indigoidpigments. We report the definitive identification of the pigments indigo and indirubin as products ofhuman cytochrome P450 (P450)-catalyzed metabolism of indole by visible, ¹H NMR, and massspectrometry. P450 2A6 was most active in the formation of these two pigments, followed by P450s2C19 and 2E1. Additional products of indole metabolism were characterized by HPLC/UV and massspectrometry. Indoxyl (3-hydroxyindole) was observed as a transient product of P450 2A6-mediatedmetabolism; isatin, 6-hydroxyindole, and dioxindole accumulated at low levels. Oxindole was thepredominant product formed by P450s 2A6, 2E1, and 2C19 and was not transformed further. A stableend product was assigned the structure 6H-oxazolo[3,2-a:4,5-b']diindole by UV, ¹H NMR, and massspectrometry, and we conclude that P450s can catalyze the oxidative coupling of indoles to form thisdimeric conjugate. On the basis of these results, we propose that the P450/NADPH-P450 reductase systemcan catalyze oxidation of indole to a variety of products.