Single oral deuterium dose useful for muscle protein synthesis by stable isotope analysis of deuterium

22 Aug Single oral deuterium dose useful for muscle protein synthesis by stable isotope analysis of deuterium

Many researchers want to measure muscle protein synthesis rates during exercise, muscle wasting diseases, or normal growth. These studies are not easy to conduct because typical protocols require continuous infusion of isotope such as 1-¹³C-leucine and stable isotope analysis of leucine in muscle proteins.

Previous protocols to measure muscle synthesis rates rely on questionable assumptions such as: (1) does the infusion of tracer stimulate protein synthesis rates? (2) what is the true precursor enrichment? For example, does stable isotope analysis of plasma KIC reflect the precursor enrichment inside the muscle cell or (3) do short-term infusions, 4-12 hours, reflect what is happening over the course of a day or week?

MacDonald et al (2013) reports a solution to measuring muscle protein synthesis without using constant infusions. The method uses a single oral dose of deuterium oxide (1 gm/kg body weight). No daily topping off after the initial bolus dosing is required. Previously, daily topping off with additional deuterium doses was utilized to measure labeling in muscle amino acids by GC/MS. A GC/MS cannot detect lower than 0.1% deuterium labeling. However, gas chromatography combustion isotope ratio mass spectrometry (GCC-IRMS) detects 0.001% deuterium enrichment in muscle amino acids. This new instrument has the capabilities to measure enrichment levels in slowly turning over proteins after single deuterium dose.

The new single bolus deuterium oxide approach allowed measurement of myofibrillar protein synthesis over two weeks with minimal disturbance to the subject. The study showed that either free body water enrichment or plasma alanine reflected the true precursor enrichment. Only a single biopsy sample collected at two weeks is required for calculating the protein synthesis rates.

Reference: MacDonald et al. (2013) A novel oral tracer procedure for measurement of myofibrillar protein synthesis.

If you would like to employ these tracer methods in your studies, please contact us for more information about our stable isotope analysis services.