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  • 标题:Intestinal HMG-CoA reductase activity is low in hypercholesterolemic patients and is further decreased with lovastatin therapy.
  • 本地全文:下载
  • 作者:M L Freeman ; W F Prigge ; D B Hunninghake
  • 期刊名称:JLR Papers In Press
  • 印刷版ISSN:0022-2275
  • 电子版ISSN:1539-7262
  • 出版年度:1988
  • 卷号:29
  • 期号:7
  • 页码:839-845
  • 语种:English
  • 出版社:American Society for Biochemistry and Molecular Biology
  • 摘要:Significant cholesterol synthesis occurs in gut mucosa of animals and humans. However, the role of gut synthesis in hypercholesterolemia and the effect of drugs on this function have not been defined. We obtained jejunal biopsies and bile samples from 21 Type II hypercholesterolemic subjects (mean serum cholesterol = 331 mg/dl) on a low fat diet after an over-night fast. Whole gut mucosal homogenate was assayed for activity of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase, the rate-determining enzyme of cholesterol synthesis. Mean reductase activity (pmol/mg per min) was 5.5 +/- 1.0 (n = 21) in hypercholesterolemic subjects versus 11.3 +/- 1.0 in 52 normal subjects (P less than 0.01). This is consistent with the hypothesis that the primary defect in these patients is not excessive cholesterol synthesis but decreased low density lipoprotein (LDL) clearance. It implies that high LDL levels down-regulate gut reductase activity. After treatment of 7 patients with lovastatin (40-80 mg/day for at least 6-13 weeks), gut reductase activity decreased from 7.7 +/- 2.6 to 3.6 +/- 0.5 (P less than 0.05), in biopsies obtained 12 hr after the last drug dose. Inhibition of reductase activity by this drug was detected 12 hr after a dose, and the enzyme was not measurably induced during 6-13 weeks of therapy. In keeping with the decrease in serum cholesterol (332----239 mg/dl) and mucosal reductase activity during lovastatin therapy, mean gallbladder bile cholesterol saturation index also decreased (1.045 +/- 0.112 vs. 0.883 +/- 0.109, n = 7).( TRUNCATED AT 250 WORDS)
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