Definition of Metabolite: Size as a Critical Criterion

Area of Science:

• Metabolomics
• Analytical Chemistry
• Bioinformatics

Background:

• The traditional definition of metabolites (<1500 Da) is challenged by new discoveries.
• Advances in analytical technology reveal larger, biologically significant molecules like polypeptides and lipopolysaccharides.

Purpose of the Study:

• To investigate the size distribution of metabolites across various databases.
• To assess the detectability of larger metabolites using current metabolomics techniques.
• To propose an updated definition of metabolites.

Main Methods:

• Analysis of multiple metabolite databases (HMDB, GNPS, PMN, NPA, MiMeDB).
• Reanalysis of liquid chromatography-mass spectrometry (LC-MS²) data from diverse biological samples, including bacteria-rich matrices.
• Examination of metabolite features beyond the 1500 Da threshold.

Main Results:

• Most metabolites are below 1000 Da, but significant populations exceed 1500 Da, particularly in bacterial datasets.
• LC-MS² data reanalysis revealed metabolite features beyond 1500 m/z in samples like feces and skin.
• Current metabolomics approaches may miss larger metabolites.

Conclusions:

• Metabolites exhibit greater size diversity than commonly recognized.
• The definition of metabolites should be revised to include larger molecules.
• Optimized mass spectrometry parameters are crucial for detecting diverse metabolite sizes.