The gut bacteria affect the bio-availability of levodopa, which is used in the treatment of Parkinson's disease. The drug is converted to dopamine that cannot cross blood-brain barrier.

‘Bacterial enzyme tyrosine decarboxylase affects the bioavailability of the drug levodopa, which necessitates an increased dosage of the drug to treat Parkinson’s disease.’

Blood-brain barrier




The drug is usually taken orally, and the levodopa is absorbed in the small intestine and then transported through the bloodstream to the brain. However, decarboxylase enzymes can convert levodopa into dopamine. In contrast to levodopa, dopamine cannot cross the blood-brain barrier, so patients are also given a decarboxylase inhibitor. 'But the levels of levodopa that will reach the brain vary strongly among Parkinson's disease patients, and we questioned whether gut microbiota were playing a role in this difference', says El Aidy.
In bacterial samples from the small intestines of rats, Aidy's Ph.D. student Sebastiaan van Kessel found activity of the bacterial tyrosine decarboxylase enzyme, which normally converts tyrosine into tyramine, but was found to also convert levodopa into dopamine. 'We then determined that the source of this decarboxylase was Enterococcus bacteria.' The researchers also showed that the conversion of levodopa was not inhibited by a high concentration of the amino acid tyrosine, the main substrate of the bacterial tyrosine decarboxylase enzyme.
Bioavailability
As Parkinson's patients are given a decarboxylase inhibitor, the next step was to test the effect of several human decarboxylase inhibitors on the bacterial enzyme. 'It turned out that, for example, the inhibitor Carbidopa is over 10,000 times more potent in inhibiting the human decarboxylase', says El Aidy.
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Vicious circle
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El Aidy concludes that the presence of the bacterial tyrosine decarboxylase enzyme can explain why some patients need more frequent dosages of levodopa to treat their motor fluctuations. 'This is considered to be a problem for Parkinson's disease patients, because a higher dose will result in dyskinesia, one of the major side effects of levodopa treatment.'
Source-Eurekalert