# Turnover Rates and Numbers of Exchangeable Hydrogens in Deuterated Water Labeled Samples

## TL;DR

This paper introduces a computational method to improve the accuracy of measuring how quickly proteins break down in living organisms using deuterated water and mass spectrometry.

## Contribution

A new computational approach is proposed to correct turnover rate variability caused by exchangeable hydrogens in peptides.

## Key findings

- Turnover rate variability is partly due to differences in the number of exchangeable hydrogens in peptides.
- The proposed computational method reduces variability and improves the accuracy of turnover rate estimation.
- This approach enhances biological interpretability and supports better understanding of disease mechanisms.

## Abstract

Metabolic labeling with deuterated water is used in combination with liquid-chromatography coupled with mass spectrometry to study the turnover rates of individual proteins in vivo. This technique and bioinformatics tools for data analysis quantify the turnover rates of thousands of proteins. Turnover rates change during organismal growth and respond to alterations in the environment and diet. The accurate and statistically significant determination of the turnover rate changes of a protein depend on the variations in the turnover rates of the peptides of the protein. One of the systematic factors contributing to this variability is the dependence of the turnover rates on the number of exchangeable hydrogens of the peptides. This variability (by reducing the statistical power) reduces biological interpretability. Here, we propose a computational approach to eliminate the dependence of the turnover rates on the number of exchangeable hydrogens. This approach enhances the accuracy of turnover rate estimation and may help to support more accurate assessments of biological dynamics and disease mechanisms.