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

BACKGROUND

Positron emission tomography with L-[methyl-11C]methionine provides a measure of regional protein synthesis rate (PSR) in skeletal muscle. However, the validity of the method depends on incorporation of methionine into protein with minimal transamination, transmethylation, or both. To test directly these assumptions, uptake of L-[methyl-14C]methionine in skeletal muscle was measured in control and cycloheximide-treated rats.

METHODS

Normal and cycloheximide-treated rats (n = 8/group) were injected with 50 microCi of L-[methyl-14C]methionine and arterial blood sampled over 90 minutes. After killing, thigh muscle was homogenized, centrifuged, and treated with trichloroacetic acid. PSR from circulating methionine was estimated from trichloroacetic acid-precipitable radioactivity, arterial time-activity curves, and plasma methionine concentrations.

RESULTS

In normal rats, approximately 70% of the tissue radioactivity was precipitated with trichloroacetic acid. In normal animals, PSR was 0.22 nmoles x min(-1) x g(-1), in excellent agreement with previous results. In the cycloheximide-treated group, PSR was 0.0032 nmoles x min(-1) x g(-1); approximately 98% reduction compared with controls.

CONCLUSION

These studies support the hypothesis that L-[methyl-11(14C]methionine accumulates in skeletal muscle as 11(14)C-labeled protein.