The long term objective is to determine the manner and rate at which deuterated analogs of selected carotenoids are absorbed and disappear from the plasma of human subjects.
Specific aims are: 1) To synthesize and to characterize deuterated beta-carotene, lycopene and 8'-beta-apocarotenal. 2) To model the in vivo kinetics of the appearance in, and disappearance from, the plasma of orally administered doses of these deuterated compounds in corn oil by use of GC/MS. 3) To ascertain the appearance of specific deuterated metabolites in the plasma after dosing with a given substrate, e.g. retinol, beta-apocarotenols and their esters from beta-carotene; retinol (and its ester) and shorter beta-apocarotenols from 8' - beta-apocarotenal; and whatever major products, if any, are formed from lycopene. 4) To determine the distribution of specific carotenoids and of vitamin A metabolites in the tissues of human accident victims or surgical subjects. These observations will be correlated with the in vivo kinetic studies. These studies should provide insight into the dynamics of the intestinal absorption and of the plasma clearance or selected carotenoids in humans. Information should also be gained about the possible asymmetric cleavage, metabolism and tissue distribution of the selected carotenoids in humans. The use of completely benign deuterated analogs allows such studies to be conducted without risk to the volunteer subjects.
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