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In addition, when circulating L-carnitine concentration increases, as in the case of oral supplementation, renal reabsorption of L-carnitine may become saturated, resulting in increased urinary excretion of L-carnitine (5)
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Regarding the affinity of the fluoro compound 27 , it was anticipated that the hydroxyl group of the tyrosine side chain of 25 makes a hydrogen-bond with Glu494 of IRAP, an interaction that is lost in the case of 27 according to the free energy perturbation (FEP) analysis (Jespers et al., 2019), explaining the reduction in binding affinity of compound 27 as compared to the analogous compound 25
Schmidt EP, Yang Y, Janssen WJ, Gandjeva A, Perez MJ, Barthel L, Zemans RL, Bowman JC, Koyanagi DE, Yunt ZX, Smith LP, Cheng SS, Overdier KH, Thompson KR, Geraci MW, Douglas IS, Pearse DB, Tuder RM
