Estimation of 3-methylhistidine production in pigs by compartmental analysis

Direct in vivo methodology is not available to accurately evaluate muscle turnover in pigs. Urinary 3-methylhistidine (3MH) excretion, which is used as an in vivo marker of muscle protein breakdown in humans and cattle, is not a valid indicator for pigs. The present study proposes that data from a single bolus dose of 3-[methyl-2H3]methylhistidine tracer can mathematically describe 3MH metabolism in pigs. Plasma concentration of the tracer is described by a linear time-invariant three-compartment model by using the SAAM/CONSAM computer modeling program. The model defines masses and fluxes of 3MH within the pigs and, in particular, the intracellular de novo production of 3MH, which should reflect muscle proteolysis. The de novo production of 3MH as calculated by the model was 621 mumol/d, corresponding to a fractional breakdown rate of 2.28%/d, which is similar to values reported by using indirect methodology. These data also suggest that certain model compartments may be indicators of body muscle mass (mass of compartment 3, r = .59, P = .006). The mathematical model developed does not depend on urine collections and can be used to assess changes in muscle proteolysis in vivo.