ACETYLATION TURNS LEUCINE INTO A DRUG BY MEMBRANE TRANSPORTER SWITCHING

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. 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 ubiquitous tissue expression of MCT1 make it well suited for uptake and distribution of N‐acetyl‐l‐leucine. MCT1‐mediated uptake of a N‐acetyl‐l‐leucine as a prodrug of leucine bypasses LAT1, the rate‐limiting step in activation of leucine‐mediated signalling and metabolic process inside cells such as mTOR. Nature Scientific Reports.

IntraBio
Privacy Policy Cookies Policy ©2024 IntraBio. All rights reserved.