TY - JOUR
T1 - Low-density lipoprotein metabolism in cerebrotendinous xanthomatosis
AU - Ballantyne, Christie M.
AU - Vega, Gloria L
AU - East, Cara
AU - Richards, Glen
AU - Grundy, Scott M
N1 - Funding Information:
From the Departments of Internal Medicine and Biochemistry and the Center for Human Nutrition, University of Texas Health Science Center Dallas. Supported by the Veterans Administration, Grant No. HL 29252 (NfH/HDS/DHHS), NIH Grant No. MOI-RR00633 (General Clinical Research Center), USPHS training Grant No. AM07307. the Southwestern Medical Foundation, and the Moss Heart Foundation, Dallas. Address reprint requests to Scott h4. Grundy. MD, PhD, Center for Human Nutrition, University of Texas Health Science Center, 5323 Harry Hines Blvd, Dallas, TX 75235. o 1987 by Grune & Stratton, Inc. 0026-0495/87/3603_OOI I$O3.00/0
PY - 1987/3
Y1 - 1987/3
N2 - Cerebrotendinous xanthomatosis (CTX) is a rare disorder characterized by a defect in conversion of cholesterol into bile acids, increased plasma levels of cholestanol, and accumulations of sterols in tendons, brain, and coronary arteries. Despite the presence of tendon xanthomas, patients with CTX frequently have low levels of plasma cholesterol and low density lipoproteins (LDL). The mechanisms for a low LDL are not understood. The present study, therefore, was carried out to examine the metabolism of LDL in a 58-year-old black man with CTX. This particular patient had an LDL-cholesterol in the mid-normal range (149 ± 6 mg/dL). Nonetheless, his fractional catabolic rate (FCR) for LDL-apolipoprotein (apo-LDL) was 0.45 pools/d, which was increased compared to 15 aged-matched men (FCR, 0.30 ± 0.01 pools/d). His production rate for apo-LDL (18.5 mg/kg-d) also was increased compared to those of middle-aged men (13.5 ± 2.5 mg/kg-d). Since the underlying defect in CTX can be reversed by administration of chenodeoxycholic acid (chenodiol), the patient was treated with chenodiol (250 mg 4 × daily), and measurements of LDL kinetics were repeated. During chenodiol therapy, his LDL-cholesterol concentration rose significantly to 165 ± 12 mg/dL; his FCR for apo-LDL fell to 0.29 pools/d; and his production rate of apo-LDL declined to 14.4 mg/kg-d. We postulate that chenodiol suppressed the excessive synthesis of cholesterol and bile acids, which had two effects. It curtailed both the overproduction of LDL and the excessive synthesis of LDL receptors, the latter being responsible for the high FCR of apo-LDl in the untreated state.
AB - Cerebrotendinous xanthomatosis (CTX) is a rare disorder characterized by a defect in conversion of cholesterol into bile acids, increased plasma levels of cholestanol, and accumulations of sterols in tendons, brain, and coronary arteries. Despite the presence of tendon xanthomas, patients with CTX frequently have low levels of plasma cholesterol and low density lipoproteins (LDL). The mechanisms for a low LDL are not understood. The present study, therefore, was carried out to examine the metabolism of LDL in a 58-year-old black man with CTX. This particular patient had an LDL-cholesterol in the mid-normal range (149 ± 6 mg/dL). Nonetheless, his fractional catabolic rate (FCR) for LDL-apolipoprotein (apo-LDL) was 0.45 pools/d, which was increased compared to 15 aged-matched men (FCR, 0.30 ± 0.01 pools/d). His production rate for apo-LDL (18.5 mg/kg-d) also was increased compared to those of middle-aged men (13.5 ± 2.5 mg/kg-d). Since the underlying defect in CTX can be reversed by administration of chenodeoxycholic acid (chenodiol), the patient was treated with chenodiol (250 mg 4 × daily), and measurements of LDL kinetics were repeated. During chenodiol therapy, his LDL-cholesterol concentration rose significantly to 165 ± 12 mg/dL; his FCR for apo-LDL fell to 0.29 pools/d; and his production rate of apo-LDL declined to 14.4 mg/kg-d. We postulate that chenodiol suppressed the excessive synthesis of cholesterol and bile acids, which had two effects. It curtailed both the overproduction of LDL and the excessive synthesis of LDL receptors, the latter being responsible for the high FCR of apo-LDl in the untreated state.
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U2 - 10.1016/0026-0495(87)90187-9
DO - 10.1016/0026-0495(87)90187-9
M3 - Article
C2 - 3821507
AN - SCOPUS:0023111102
SN - 0026-0495
VL - 36
SP - 270
EP - 276
JO - Metabolism
JF - Metabolism
IS - 3
ER -