Etomoxir-carnitine, a novel pharmaco-metabolite of etomoxir, inhibits phospholipases A₂ and mitochondrial respiration.

ABSTRACT: Mitochondrial fatty acid oxidation serves as an essential process for cellular survival, differentiation, proliferation, and energy metabolism. Numerous studies have utilized etomoxir (ETO) for the irreversible inhibition of carnitine palmitoylcarnitine transferase 1 (CPT1), which catalyzes the rate-limiting step for mitochondrial long-chain fatty acid β-oxidation to examine the bioenergetic roles of mitochondrial fatty acid metabolism in many tissues in multiple diverse disease states. Herein, we demonstrate that intact mitochondria robustly metabolize ETO to etomoxir-carnitine (ETO-carnitine) prior to nearly complete ETO-mediated inhibition of CPT1. The novel pharmaco-metabolite, ETO-carnitine, was conclusively identified by accurate mass, fragmentation patterns, and isotopic fine struct

SUBMITTER: Moon SH 

PROVIDER: S-EPMC11402452 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature