Isotope-Assisted Metabolic Flux Analysis: A Powerful Technique to Gain New Insights into the Human Metabolome in Health and Disease

Abstract

Cell metabolism represents the coordinated changes in genes, proteins, and metabolites that occur in health and disease. The metabolic fluxome, which includes both intracellular and extracellular metabolic reaction rates (fluxes), therefore provides a powerful, integrated description of cellular phenotype. However, intracellular fluxes cannot be directly measured. Instead, flux quantification requires sophisticated mathematical and computational analysis of data from isotope labeling experiments. In this review, we describe isotope-assisted metabolic flux analysis (iMFA), a rigorous computational approach to fluxome quantification that integrates metabolic network models and experimental data to generate quantitative metabolic flux maps. We highlight practical considerations for implementing iMFA in mammalian models, as well as iMFA applications in in vitro and in vivo studies of physiology and disease. Finally, we identify promising new frontiers in iMFA which may enable us to fully unlock the potential of iMFA in biomedical research.

Metabolomics of infectious diseases in the era of personalized medicine

“…Their impact can be observed by measuring the frequency of integration of an isotopically labelled substrate such as 13 C-glucose into a biological system of organisms, cells or animals. (Moiz et al, 2022). Metabolomic flux analysis has been deployed to investigate the effect of the drug Bedaquiline (BDQ) in antibiotic resistant strain of Mycobacterium tuberculosis (Mtb).…”

“…Flux is calculated based on the experimental external fluxes, mass distribution vectors (MDV) and a metabolic map that highlights all relevant reactions. Software such as, eiFlux, INCA, METRAN, OpenMedius and 13C2FLUX are used to support the metabolic model, flux estimation, and confidence interval calculation ( Moiz et al, 2022 ). Metabolomic flux analysis has been deployed to investigate the effect of the drug Bedaquiline (BDQ) in antibiotic resistant strain of Mycobacterium tuberculosis (Mtb).…”

“…Metabolomic flux analysis has been deployed to investigate the effect of the drug Bedaquiline (BDQ) in antibiotic resistant strain of Mycobacterium tuberculosis (Mtb). MFA has also been used to study the metabolic changes in host cell during viral infection ( Moiz et al, 2022 ).…”