Turnover Rate of Lipids, Metabolites and Proteins Revealed by 156-Day-Long D₂O Administration in a Guinea Pig

Measurement of the turnover rate of proteins, different metabolites and lipids in living organisms is important for the understanding of biochemical pathways and physiology studies. Such experiments can be performed by administering isotopically labeled substances (food or water) to the organism and measuring the amount of the isotopes in the endogenous compounds. Here, we administered 20% heavy water (D₂O) to a guinea pig for 156 days and regularly measured the deuterium uptake in C-H groups in the different compounds of blood, urine and feces using high-resolution mass spectrometry. We successfully measured the time required for reaching the maximum deuteration level for several classes of compounds: 10 days for blood lipids (PC, PE, TAG); 60 days for sterol derivatives, heme B and hemoglobin; and 70 days for stercobilin. Also, for those compounds, we measured the deuterium elimination time from the organism when deuterium administration was stopped. The turnover of lipids was also studied by administering deuterated oat leaves grown at 10% D₂O to the guinea pig. The analysis of blood revealed that triglycerides demonstrate the inclusion of the deuterium after 5 h. All experiments were performed on a single guinea pig that remained alive and in good health after all experiments. The current research demonstrates the possibility of using long-term D₂O administration for the investigation of metabolism.