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Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism.
- Source :
-
Science (New York, N.Y.) [Science] 2019 Jun 14; Vol. 364 (6445). - Publication Year :
- 2019
-
Abstract
- 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.<br /> (Copyright © 2019, American Association for the Advancement of Science.)
- Subjects :
- 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
Actinobacteria enzymology
Antiparkinson Agents metabolism
Bacterial Proteins metabolism
Enterococcus faecalis enzymology
Gastrointestinal Microbiome genetics
Levodopa metabolism
Tyrosine analogs & derivatives
Tyrosine Decarboxylase metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9203
- Volume :
- 364
- Issue :
- 6445
- Database :
- MEDLINE
- Journal :
- Science (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 31196984
- Full Text :
- https://doi.org/10.1126/science.aau6323