A quantitative metabolic defect in lipid metabolism associated with abnormal serum lipoproteins in man.

Tritium-labeled cholesterol has been fed to a selected series of patients to demonstrate a quantitative metabolic defect in lipid metabolism in the presence of abnormal serum lipoprotein spectra. Patients with abnormal serum lipoprotein spectra carry a greater fraction of their newly absorbed cholesterol in the esterified form than do normals. THE LIPOPROTEINS of human serum are conveniently defined and quantitated in the ultracentrifuge according to their flotation rates under carefully defined conditions .' Inasmuch as the concentration of certain serum lipoprotein molecules so defined (Sf 12-20; Sf 20-100*) show a positive correlation with the incidence of human atherosclerosis,2 those factors which determine the lipoprotein spectrum of the serum in any individual become of potential importance in understanding the pathologic physiology of atherosclerosis. A search for determining factors important in lipoprotein metabolism logically includes several varied aspects of cholesterol metabolism. The interrelationships between serum lipo-protein spectra and oral cholesterol metabolism are under investigation in this study. Labeled cholesterol has been administrated to a series of 10 patients, and it has been possible to demonstrate a quantitative metabolic defect in lipid metabolism in patients who have abnormal ultracentrifugal lipoprotein spectra. Atomic Energy Commission. * Units are Svedbergs of flotation (Sf). One Sf unit equals a migration rate of 10-1' cm./sec./dyne/ Gm. at 26 C. in a medium of sodium chloride solution of density 1.063. 393 Tritium-labeled cholesterol' has been fed to 10 selected patients: two with xanthoma tuberosum, two with xanthoma tendinosum, three with clinical atherosclerosis, and three normals. Patients with xanthomata have been used in four instances because they afford a unique opportunity to study extremes in lipoprotein spectra.4 Patients with xanthoma tuberosum have elevated serum cholesterol values associated with an extremely abnormal ultracentrifuge pattern; the lipoprotein spectrum approaches that seen in cholesterol-fed rabbits. In xanthoma tendinosum, on the other hand, there is also a hypercholesterolemia but here the ultracentrifuge lipoprotein spectrum is of particular interest in that the hyperlipo-proteinemia remains almost entirely within the Sf 0-12 class of lipoprotein molecules. The 10 patients selected then afford a sampling over a wide range of lipoprotein spectra. Besides providing a wide range of serum lipoprotein spectra the patients also provide wide variations in serum cholesterol values as well. Within the 10 patients of the group, however, there is no correlation between the level of serum cholesterol and the type of centrifuge pattern found. As a result it has been possible to evaluate …