Measurement of muscle protein synthesis by positron emission tomography with L-[methyl-C-11]methionine: Effects of transamination and transmethylation

Background: Positron emission tomography with L-[methyl-C-11]methionine pro vides a measure of regional protein synthesis rate (PSR) in skeletal muscle . However, the validity of the method depends on incorporation of methionin e into protein with minimal transamination, transmethylation, or both. To t est directly these assumptions, uptake of L-[methyl-C-14]methionine in skel etal muscle was measured in control and cycloheximide-treated rats. Methods: Normal and cycloheximide-treated rats (n = 8/group) were injected with 50 mu Ci of L-[methyl-C-14]methionine and arterial blood sampled over 90 minutes. After killing, thigh muscle was homogenized, centrifuged, and t reated with trichloroacetic acid. PSR from circulating methionine was estim ated from trichloroacetic acid-precipitable radioactivity, arterial time-ac tivity curves, and plasma methionine concentrations. Results: In normal rats, similar to 70% of the tissue radioactivity was pre cipitated with trichloroacetic acid. In normal animals, PSR was 0.22 nmoles .min(-1).g(-1), in excellent agreement with previous results. In the cycloh examide-treated group, PSR was 0.0032 nmoles.min(-1).g(-1); similar to 98% reduction compared with controls. Conclusion: These studies support the hypothesis that L-[methyl-C-11(14)]me thionine accumulates in skeletal muscle as C-11(14)-labeled protein.