Characterization of human plasma proteome dynamics using deuterium oxide

Area of Science:

• Biochemistry
• Proteomics
• Human Physiology

Background:

• High-throughput quantification of human protein turnover offers insights into disease mechanisms.
• In vivo deuterium oxide ((2)H2O) administration is a promising technique for this analysis.
• Clinical translation requires safety and hemodynamic characterization of (2)H2O administration.

Purpose of the Study:

• To evaluate the safety, feasibility, efficacy, and reproducibility of (2)H2O intake in healthy human subjects.
• To establish a protocol for deuterium enrichment in body water and proteins.
• To measure plasma proteome dynamics using advanced mass spectrometry.

Main Methods:

• Ten healthy, demographically diverse subjects participated in the study.
• Subjects orally consumed weight-adjusted doses of 70% (2)H2O daily for 14 days.
• Plasma proteome dynamics were analyzed using a high-resolution mass spectrometry method.

Main Results:

• The protocol was successfully implemented in all ten subjects.
• Endogenous turnover rates for 542 human plasma proteins were characterized, representing the largest dataset to date.
• No adverse physiological effects or discomfort were observed during (2)H2O consumption.

Conclusions:

• The (2)H2O intake protocol is safe, accessible, and effective for clinical investigations of human protein turnover.
• This workflow demonstrates significant translational value for studying plasma protein dynamics in human diseases.
• The findings support the use of this method for large-scale proteomic research.