title: Recent advances for measurement of protein synthesis rates, use of the 'Virtual Biopsy' approach, and measurement of muscle mass.
abstract: OBJECTIVE
  Flux-rate measurements of protein synthesis and breakdown (turnover) in muscle represent an ideal class of mechanism-based biomarkers for conditions of altered muscle mass and function. We describe here new metabolic labeling techniques for flux-rate measurements in humans, focusing on skeletal muscle.
  
  
  RESULTS
  Dynamics of the muscle proteome are accurately measured in humans by combining long-term heavy water labeling with tandem mass spectrometry. Broad proteomic flux signatures or kinetics of targeted proteins are measurable. After interventions, early fractional synthesis rates of skeletal muscle proteins predict later changes in muscle mass. The 'virtual biopsy' method for measuring tissue protein turnover rates from body fluids has been validated for skeletal muscle, from labeling of plasma creatine kinase-type M or carbonic anhydrase-3. Label in these proteins in plasma reflects label of cognate proteins in the tissue, and response in plasma predicts longer term outcomes. Skeletal muscle mass can also be measured noninvasively from a spot urine, based on dilution of labeled creatine. This method correlates well with whole body MRI assessment of muscle mass and predicts clinical outcomes in older men.
  
  
  CONCLUSIONS
  Flux measurements are available and more interpretable functionally than static measurements for several reasons, which are discussed.
authors.affiliation: aNutritional Sciences and Toxicology, University of California at Berkeley, Berkeley bEndocrinology, Metabolism and Nutrition, University of California at San Francisco, San Francisco, California cDivision of Geriatrics, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Hellerstein
authors.forename: William
authors.initials: W
authors.lastname: Evans
mesh_terms: D001706:Biopsy / Q000379:methods; D001834:Body Water / Q000378:metabolism; D006801:Humans; D009124:Muscle Proteins / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009135:Muscular Diseases / Q000175:diagnosis; D014176:Protein Biosynthesis / Q000502:physiology*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D013194:Staining and Labeling / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D009124:Muscle Proteins; D020543:Proteome