{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Churchill GC"],"funding":["IntraBio","Wellcome Trust"],"pagination":["15812"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8338929"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(1)"],"pubmed_abstract":["Small changes to molecules can have profound effects on their pharmacological activity as exemplified by the addition of the two-carbon acetyl group to make drugs more effective by enhancing their pharmacokinetic or pharmacodynamic properties. N-acetyl-D,L-leucine is approved in France for vertigo and its L-enantiomer is being developed as a drug for rare and common neurological disorders. However, the precise mechanistic details of how acetylation converts leucine into a drug are unknown. Here we show that acetylation of leucine switches its uptake into cells from the L-type amino acid transporter (LAT1) used by leucine to organic anion transporters (OAT1 and OAT3) and the monocarboxylate transporter type 1 (MCT1). Both the kinetics of MCT1 (lower affinity compared to LAT1) and the ubiqui"],"journal":["Scientific reports"],"pubmed_title":["Acetylation turns leucine into a drug by membrane transporter switching."],"pmcid":["PMC8338929"],"funding_grant_id":["202834/Z/16/Z"],"pubmed_authors":["Bremova-Ertl T","Strupp M","Churchill GC","Factor C","Factor M","Galione A","Patterson MC","Platt FM"],"additional_accession":[]},"is_claimable":false,"name":"Acetylation turns leucine into a drug by membrane transporter switching.","description":"Small changes to molecules can have profound effects on their pharmacological activity as exemplified by the addition of the two-carbon acetyl group to make drugs more effective by enhancing their pharmacokinetic or pharmacodynamic properties. N-acetyl-D,L-leucine is approved in France for vertigo and its L-enantiomer is being developed as a drug for rare and common neurological disorders. However, the precise mechanistic details of how acetylation converts leucine into a drug are unknown. Here we show that acetylation of leucine switches its uptake into cells from the L-type amino acid transporter (LAT1) used by leucine to organic anion transporters (OAT1 and OAT3) and the monocarboxylate transporter type 1 (MCT1). Both the kinetics of MCT1 (lower affinity compared to LAT1) and the ubiqui","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Aug","modification":"2026-05-08T06:29:09.382Z","creation":"2022-02-11T14:20:14.338Z"},"accession":"S-EPMC8338929","cross_references":{"pubmed":["34349180"],"doi":["10.1038/s41598-021-95255-5"]}}