New collaborative #scientificposter on #lysosomes presented this week at the GRC Drug Metabolism Conference: https://lnkd.in/eb9rrbDP Understanding the distribution and abundance of #drugtargets, metabolizing #enzymes, and #drugtransporters within liver subcellular compartments is crucial for #drugmetabolism and #toxicity studies. This study focused on identification and quantification using global quantitative #proteomics analysis.
Human liver lysosomes Biologics entering the cells by receptor-mediated uptake, e.g., antibody drug conjugates and related targeted modalities, are processed in the vesicles of endosomal-lysosomal pathway and can be catabolized in lysosomes. Specific metabolic reactions performed by lysosomal enzymes are essential for proper release and pharmacological activity of biologic’s payloads. In their catabolic capacity lysosomal enzymes act as a “microsomes for biologics”. Plurality of hydrolases contained in human liver lysosomes is scarcely characterized for metabolic activity, abundance, and regulation. Similarly, variability of these enzymes in individual donors and multiple organs has not been characterized. Dr. Prasad Research Group (https://pharmacy.wsu.edu/) provided proteomic characterization of BioIVT human liver lysosomes (HLL) from 15 donors (https://lnkd.in/gMgGSHTQ). Major findings of the work, presented this week at Gordon Research Conference (https://lnkd.in/gTdsdMBb) are 1) lysosomal markers (e.g., HEXA, HEXB, ACP2, and GUSB) are highly enriched and abundant in lysosomal preparation but not detected in human liver microsomes, 2) endoplasmic reticulum markers and mitochondrial markers are also detected in the lysosomal reparations, 3) multiple drug metabolizing enzymes and transporters are also enriched in HLL. These data enable proper design and interpretation of results of studies elucidating catabolism of biologics in lysosomes.