Metabolic mechanisms of a drug revealed by distortion-free ¹³C tracer analysis.

ABSTRACT: Metabolomic isotopic tracing can provide flux information useful for understanding drug mechanisms. For that, NMR has the unique advantage of giving positional isotope enrichment information, but the current ¹³C 1D NMR approach suffers from low sensitivity and high overlaps. We developed a new 2D heteronuclear NMR experiment incorporating J-scaling and distortion-free elements that allows for quantitative analysis of multiplets with high sensitivity and resolution. When applied to an old chemotherapeutic drug, the approach provided a quantitative estimation of TCA-cycle turns, confirming the conventional mechanism of its mitochondrial metabolic enhancement. Additionally, the approach identified a new mechanism of the higher contribution of the pentose phosphate pathway to

SUBMITTER: Cha JW 

PROVIDER: S-EPMC8179602 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature