Increased sitosterol absorption is offset by rapid elimination to prevent accumulation in heterozygotes with sitosterolemia.
- 1 May 1992
- journal article
- case report
- Published by Ovid Technologies (Wolters Kluwer Health) in Arteriosclerosis and Thrombosis: A Journal of Vascular Biology
- Vol. 12 (5), 563-568
- https://doi.org/10.1161/01.atv.12.5.563
Abstract
Using plasma isotope-kinetic methods, we measured the absorption and turnover rates of cholesterol and sitosterol (24-ethylcholesterol) in two obligate heterozygotes (parents) and their homozygous daughter with sitosterolemia with xanthomatosis. Diets contained approximately 500 mg/day cholesterol and 100 mg/day sitosterol. In the homozygote, plasma cholesterol and apolipoprotein B concentrations were slightly higher, but sitosterol levels were 22 and 58 times higher than in her heterozygous parents. Cholesterol absorption was at the high end of the normal range in both heterozygotes (59% and 84%) and in the homozygote (62%) (value in the control subject 48%). In contrast, cholesterol synthesis was severely depressed in the homozygote (28% and 26% as great as in the heterozygotes and the control, respectively). Sitosterol absorption in the homozygote (34%) was 2.3 and 2.0 times greater than in the heterozygotes and 6.8 times greater than in the control. The sitosterol turnover rate, calculated independently by mathematical analysis of specific-activity decay curves, amounted to 15 and 24 mg/day in the heterozygotes compared with 27 mg/day in the homozygote and 7.9 +/- 2.3 mg/day in five control subjects. However, the total body sitosterol pool was 15 and 10.3 times larger in the homozygote (4,080 mg) than in her heterozygous parents because of extremely slow removal. The average sitosterol elimination constant in the heterozygotes (KA = 0.11 day-1) was 10 times that in the homozygote (KA = 0.01 day-1) but 35% less than that in the controls (KA = 0.17 day-1).(ABSTRACT TRUNCATED AT 250 WORDS)Keywords
This publication has 19 references indexed in Scilit:
- A molecular defect in hepatic cholesterol biosynthesis in sitosterolemia with xanthomatosis.JCI Insight, 1990
- Unexpected failure of bile acid malabsorption to stimulate cholesterol synthesis in sitosterolemia with xanthomatosis. Comparison with lovastatin.Arteriosclerosis: An Official Journal of the American Heart Association, Inc., 1990
- Heterogeneity of cholesterol homeostasis in man. Response to changes in dietary fat quality and cholesterol quantity.JCI Insight, 1987
- Increased Concentrations of Cholestanol and Apolipoprotein B in the Cerebrospinal Fluid of Patients with Cerebrotendinous XanthomatosisNew England Journal of Medicine, 1987
- Abnormal metabolism of shellfish sterols in a patient with sitosterolemia and xanthomatosis.JCI Insight, 1986
- The presence of 5α-sitostanol in the serum of a patient with phytosterolemia, and its biosynthesis from plant steroids in rats with bile fistulaBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1985
- Identification of 5α-stanols in patients with sitosterolemia and xanthomatosis: stereochemistry of the protonolysis of steroidal organoboranes.Steroids, 1982
- Phytosterolaemia, xanthomatosis and premature atherosclerotic arterial disease: a case with high plant sterol absorption, impaired sterol elimination and low cholesterol synthesisEuropean Journal of Clinical Investigation, 1980
- Long-term decay of serum cholesterol radioactivity: body cholesterol metabolism in normals and in patients with hyperlipoproteinemia and atherosclerosisJCI Insight, 1970
- Turnover of plasma cholesterol in manJCI Insight, 1968