Human cholesterol synthesis measurement using deuterated water: Theoretical and procedural considerations

Abstract

Human cholesterogenesis is measurable as the rate of incorporation of deuterium derived from deuterium oxide (D2O) within the body water pool into plasma or erythrocyte cholesterol pools. Oral D2O equilibrates across body water, thus enabling extracellular sampling of pools (such as urine) to serve as accurate indicators of intracellular deuterium enrichments at the point of synthesis. Required doses of D2O fall below the threshold associated with negative side effects. Deuterium/carbon incorporation ratios into cholesterol during biosynthesis have been established that are applicable in humans. Models using unconstrained and constrained curve fitting permit improved flexibility in interpretation of deuterium-uptake kinetics. However, sample-size restrictions presently limit the ability of the technique to examine the kinetics within individual lipoprotein species. Correction of enrichment data for proton exchange during the combustion and reduction phases of sample preparation is an additional important procedural concern. In summary, the deuterated-water procedure is a useful tool in studies of human cholesterol synthesis that offers the advantages of short measurement interval, relative noninvasiveness, and provision of a direct index of synthesis in comparison with other available techniques.