Estimating protein turnover with a [15N,13C]leucine tracer: a study using simulated data.
We explore the use of [15N,13C]leucine tracer to estimate whole-body fractional rates of a fast-turning-over protein pool employing synthetic data. The kinetics of [15N,13C]leucine tracer are simplified compared with those of traditional leucine tracers and benefit from irreversible transamination to [13C]alpha-ketoisocaproaic acid (KIC) resulting in a simplified model structure. A three-compartment model of [15N,13C]leucine kinetics was proposed and evaluated using data generated by a Reference Model (based on a model by Cobelli et al.). The results suggest that fractional turnover rates of a fast-turning-over protein pool can be estimated with a low but acceptable precision during a six-hour constant intravenous infusion of [15N,13C]leucine with frequent sampling of plasma tracer-to-tracee ratio (TTR) of [15N,13C]leucine. We conclude that [15N,13C]leucine may be useful for the measurement of protein kinetics and its full potential should be explored in clinical studies with compartmental data analysis.
Gowrie
I J
IJ
Centre for Measurement and Information of Medicine, City University, Northampton Square, London, EC1V 0HB, U.K.
Roudsari
A V
AV
Umpleby
A M
AM
Hovorka
R
R
D002247:Carbon Isotopes; D003198:Computer Simulation; D005215:Fasting / Q000378:metabolism*; D006801:Humans; D007651:Keto Acids / Q000378:metabolism; D007930:Leucine / Q000378:metabolism; D008954:Models, Biological; D009587:Nitrogen Isotopes; D011506:Proteins / Q000378:metabolism*
D002247:Carbon Isotopes; D007651:Keto Acids; D009587:Nitrogen Isotopes; D011506:Proteins; C013082:alpha-ketoisocaproic acid; D007930:Leucine