دورية أكاديمية
أعرض في EDS

Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism.

التفاصيل البيبلوغرافية
العنوان: Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism.
المؤلفون: Maini Rekdal V; Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA., Bess EN; Department of Microbiology and Immunology, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.; Department of Chemistry, University of California, Irvine, 1102 Natural Sciences 2, Irvine, CA 92617, USA.; Department of Molecular Biology and Biochemistry, University of California, Irvine, 1102 Natural Sciences 2, Irvine, CA 92617, USA., Bisanz JE; Department of Microbiology and Immunology, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA., Turnbaugh PJ; Department of Microbiology and Immunology, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA. balskus@chemistry.harvard.edu peter.turnbaugh@ucsf.edu.; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA., Balskus EP; Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA. balskus@chemistry.harvard.edu peter.turnbaugh@ucsf.edu.
المصدر: Science (New York, N.Y.) [Science] 2019 Jun 14; Vol. 364 (6445).
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 0404511 Publication Model: Print Cited Medium: Internet ISSN: 1095-9203 (Electronic) Linking ISSN: 00368075 NLM ISO Abbreviation: Science Subsets: MEDLINE
أسماء مطبوعة: Publication: : Washington, DC : American Association for the Advancement of Science
Original Publication: New York, N.Y. : [s.n.] 1880-
مواضيع طبية MeSH: Gastrointestinal Microbiome*/genetics, Actinobacteria/*enzymology , Antiparkinson Agents/*metabolism , Bacterial Proteins/*metabolism , Enterococcus faecalis/*enzymology , Levodopa/*metabolism , Tyrosine/*analogs & derivatives , Tyrosine Decarboxylase/*metabolism, Actinobacteria/drug effects ; Actinobacteria/genetics ; Animals ; Antiparkinson Agents/administration & dosage ; Bacterial Proteins/antagonists & inhibitors ; Bacterial Proteins/genetics ; Decarboxylation/drug effects ; Dopamine/metabolism ; Enterococcus faecalis/drug effects ; Enterococcus faecalis/genetics ; Genome, Bacterial ; HeLa Cells ; Humans ; Levodopa/administration & dosage ; Male ; Metabolic Networks and Pathways/drug effects ; Mice, Inbred BALB C ; Tyrosine/administration & dosage ; Tyrosine/chemistry ; Tyrosine/pharmacology ; Tyrosine Decarboxylase/antagonists & inhibitors ; Tyrosine Decarboxylase/genetics
مستخلص: The human gut microbiota metabolizes the Parkinson's disease medication Levodopa (l-dopa), potentially reducing drug availability and causing side effects. However, the organisms, genes, and enzymes responsible for this activity in patients and their susceptibility to inhibition by host-targeted drugs are unknown. Here, we describe an interspecies pathway for gut bacterial l-dopa metabolism. Conversion of l-dopa to dopamine by a pyridoxal phosphate-dependent tyrosine decarboxylase from Enterococcus faecalis is followed by transformation of dopamine to m -tyramine by a molybdenum-dependent dehydroxylase from Eggerthella lenta These enzymes predict drug metabolism in complex human gut microbiotas. Although a drug that targets host aromatic amino acid decarboxylase does not prevent gut microbial l-dopa decarboxylation, we identified a compound that inhibits this activity in Parkinson's patient microbiotas and increases l-dopa bioavailability in mice.
(Copyright © 2019, American Association for the Advancement of Science.)
التعليقات: Comment in: Science. 2019 Jun 14;364(6445):1030-1031. (PMID: 31196998)
Comment in: Cell Metab. 2019 Aug 6;30(2):235-237. (PMID: 31390549)
Comment in: Parkinsonism Relat Disord. 2019 Sep;66:265-266. (PMID: 31445904)
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معلومات مُعتمدة: R01 HL122593 United States HL NHLBI NIH HHS; T32 GM007598 United States GM NIGMS NIH HHS; United States HHMI Howard Hughes Medical Institute
المشرفين على المادة: 0 (Antiparkinson Agents)
0 (Bacterial Proteins)
160766-13-2 (3-fluoro-alpha-fluoromethyltyrosine)
42HK56048U (Tyrosine)
46627O600J (Levodopa)
EC 4.1.1.25 (Tyrosine Decarboxylase)
VTD58H1Z2X (Dopamine)
تواريخ الأحداث: Date Created: 20190615 Date Completed: 20191119 Latest Revision: 20210116
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC7745125
DOI: 10.1126/science.aau6323
PMID: 31196984
قاعدة البيانات: MEDLINE
الوصف
تدمد:1095-9203
DOI:10.1126/science.aau6323