Skeletal muscle myosin heavy chain synthesis rate in healthy humans

Measurement of synthesis rate of specific proteins is essential to understand the regulation of protein synthesis at the molecular level. Although mixed muscle protein (MMP) synthesis rate has been previously measured in humans, individual muscle proteins have not been studied. We measured fractional synthesis rate (FSR) of myosin heavy chain (MHC), the main muscle contractile protein, in 10 healthy subjects (age 30+2.7 years, M:F: 6:4, BMI~24.6±1.9, muscle mass=30.2±l.8kg). During continuous infusion of L(1-BC) leucine, quadriceps, muscle biopsies were taken at 5h and 10h. MHC was purified from muscle protein by a continuous elution gel electrophoresîs and the purity was verified with analytical sodium dodecyl sulfate polyacrylamide gel electrophoresis and silver staining. Isotopic enrichment of MHC and MMP were determined using a GC isotope ratio mass spectrometer. Plasma (' C) ketoisocaproate was used as the surrogate of the precursor of protein synthesis. FSR of MHC (0.030+0.003%/h) was 73±4% ofthat of mixed muscle protein (0.04l±0.004%/h). Whole body protein synthesis (WBPS) was estimated from non-oxidative leucine flux and whole body muscle protein synthesis rate (WBMPS) was estimated from FSR of MMP and muscle protein mass. WBMPS (36 ±5mg/kg/h) was 29 ±4% of WBPS (127±4mg/kg/h). The whole body MHC synthesis rate (6.8±l.lmg/kg/h) was 18±1% of WBMPS and 5.4⁺0.8% of WBPS. A 25% decrease in MHC synthesis rate in sarcopenia would change WBMPS by less than 5% and less than 2% in WBPS. Measurement of the synthesis rates of mixed muscle protein or whole body protein synthesis are not sensitive to detect substantial changes in MHC. It is critical to measure synthesis rate of MHC to investigate conditions of muscle contractile disorders.