Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism
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Abstract
The dope on l -dopa metabolism The efficacy of l -dopa treatment for Parkinson's disease is hugely variable between individuals, depending on the composition of their microbiota. l -Dopa is decarboxylated into active dopamine, but if the gut microbiota metabolize l -dopa before it crosses the blood-brain barrier, medication is ineffective. Maini Rekdal et al. found that different species of bacterium are involved in l -dopa metabolism (see the Perspective by O'Neill). Tyrosine decarboxylase (TDC) from Enterococcus faecalis and dopamine dehydroxylase (Dadh) from Eggerthella lenta A2 sequentially metabolized l -dopa into m -tyramine. The microbial l -dopa decarboxylase can be inactivated by ( S )-α-fluoromethyltyrosine (AFMT), which indicates possibilities for developing combinations of Parkinson's drugs to circumvent microbial inactivation. Science , this issue p. eaau6323 ; see also p. 1030
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The record
- Venue
- Science
- Topic
- Gut microbiota and health
- Field
- Biochemistry, Genetics and Molecular Biology
- Canadian institutions
- —
- Funders
- National Institute of General Medical SciencesNational Heart, Lung, and Blood InstituteLife Sciences Research FoundationRheumatology Research FoundationNational Science FoundationDamon Runyon Cancer Research FoundationHoward Hughes Medical InstituteBill and Melinda Gates FoundationArthritis FoundationNatural Sciences and Engineering Research Council of CanadaDavid and Lucile Packard FoundationNational Institutes of HealthKinship Foundation
- Keywords
- Aromatic L-amino acid decarboxylaseGut floraEnzymeMetabolismDrug metabolismBiochemistryTyramineDecarboxylationPharmacologyMicrobial metabolismMicrobiologyChemistryBiologyBacteria
- Has abstract in OpenAlex
- yes