Stable-isotope-assisted metabolomic

Stable-isotope-assisted metabolomicsIdentification and quantification of metabolic biomarkers can provide a metabolic snapshot of the status of a living organism, but cannot provide an unambiguous picture of the metabolic flux between cellular compartments. For instance, an increase in the concentration of a metabolite can be associated with either the upregulation of the enzyme that synthesizes the metabolite or the downregulation of the one that consumes it. Stable-isotope labelling (with an isotope such as 13C) of a precursor (such as glucose or glutamine) enables tracking of its cellular fate in vitro or in vivo53,73. Datasets from such experiments can be fed into mathematical models such as metabolic flux analysis6–9,74,75 (see Supplementary information S1 (figure)).Go to:Metabolomic studies in rheumatic diseaseMetabolomics can provide important information relating to pathogenesis and disease activity in rheumatic conditions. The fundamental rationale in metabolomics is that perturbations in a biological system caused by disease will lead to correlated changes in the concentrations of certain metabolites. Although in some situations (such as genetic metabolic disease) the identification of a single, robust diagnostic metabolite migth be possible, in many others (including rheumatic disorders) the perturbations involve the activation of multiple pathways. NMR and MS can identify biomarkers and patterns of change that are highly discriminatory for these perturbations and for disease states. Disease-specific metabolic pathways can indicate potential therapeutic targets, to enable alteration of the metabolic activity implicated in pathogenesis. They can also identify disease-specific biomarkers.Biomarkers are anatomical, physiological, biochemical or molecular variables or imaging features that enable diagnosis and prognosis of disease and evaluation of the effects of treatment. The accessibility of biomarkers is important, and blood and urine are more accessible than synovial tissues or fluids in joints affected by rheumatic diseases. Despite the relative inaccessibility, metabolic profiling using intact tissue has gained momentum as an approach for understanding the molecular basis of disease.