Isotopelabeled

Isotopelabeled refers to molecules in which one or more atoms have been replaced with isotopes that are heavier or radioactive relative to the naturally occurring form. This substitution allows researchers to trace, quantify, or track the fate of the labeled species in biological, chemical, or environmental systems without significantly altering the molecule’s chemistry.

Two broad categories exist: stable isotope labeling, in which non-radioactive isotopes such as 13C, 15N, 2H (deuterium), 18O, or 34S are incorporated; and radioactive isotope labeling, which uses isotopes such as 3H, 14C, 32P, or 35S to emit detectable radiation. Stable isotopes are more common in modern research due to safety and long-term tracing advantages; radioactive labels are used when radiometric detection is advantageous or when other methods are impractical.

Common approaches include metabolic labeling of cells or organisms with labeled nutrients (for example, SILAC uses 13C or 15N-labeled amino acids to label cellular proteomes). Isotope labeling is also applied in nucleotides, metabolites, or probes, and in NMR experiments where 13C or 15N enrichment improves signal resolution.

Detection and quantification rely on mass spectrometry, which distinguishes isotopologs by mass differences and isotopic envelopes, and on NMR, which uses isotope-specific resonances and coupling patterns. Applications span quantitative proteomics, metabolic flux analysis, tracer studies in pharmacokinetics, drug metabolism, environmental tracing, and plant or microbial physiology. Isotopelabeled compounds can serve as internal standards or tracers that facilitate accurate measurement under varying conditions.

Limitations include cost and availability of labeled substrates, potential isotope effects on kinetics or metabolism, incomplete labeling or scrambling of isotopes, and the need for specialized instrumentation and data analysis to resolve isotopolog distributions. See also isotope labeling, SILAC, and metabolic flux analysis.