Model of the kinetics of ketone bodies in humans
Authors
Discussion
Loading...
Member takes
Implication
Tracer kinetic study reveals four-compartment ketone body dynamics in healthy adults, indicating that conventional turnover calculations produce substantial parameter errors.
Key Points
- Establish an accurate compartmental kinetic model to quantify in vivo ketone body production, distribution, interconversion, and clearance in humans.
- Administered combined bolus intravenous injections of [14C]acetoacetate and beta-[14C]-hydroxybutyrate to seven overnight-fasted healthy subjects on two separate occasions (N=7).
- Collected frequent serial blood samples over 100 minutes to monitor tracer kinetics.
- Analyzed kinetic data using both noncompartmental and compartmental modeling techniques to assess systemic and tissue turnover.
- Identified a physiologically plausible four-compartment model representing acetoacetate and beta-hydroxybutyrate in blood alongside liver and extrahepatic tissue compartments as the best fit for tracer data.
- Quantified liver ketone body synthesis rates from acetyl-CoA, tissue interconversion, recycling, plasma clearance rates, and initial distribution volumes.
- Revealed that conventional analytical methods using combined specific activities rely on invalid in vivo assumptions, causing substantial errors in metabolic estimates.
Cite This Study
Cobelli et al. (1982) studied this question.