The level of 7-dehydrocholesterol in plasma reflects the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the human liver

Magnus Axelson , Bo Angelin , Carl-Gustaf Hillebrant , Eva Reihnér , Curt Einarsson
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引用次数: 8

Abstract

Plasma levels of the cholesterol precursor 7-dehydrocholesterol (7-DHC) were compared with activities of the rate-limiting enzyme in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase assayed in liver biopsies from patients undergoing cholecystectomy. Some patients were treated with cholestyramine, deoxycholic acid or chenodeoxycholic acid prior to surgery in order to alter the activity of the enzyme. The median level of 7-DHC and the activity of HMG-CoA reductase in the untreated group were 55 ng/ml and 98 pmol/min/mg protein, respectively. The sterol levels and enzyme activities were increased in patients treated with cholestyramine (85 ng/ml and 439 pmol/min/mg protein) and deoxycholic acid (86 ng/ml and 173 pmol/min/mg protein) and decreased in patients treated with chenodeoxycholic acid (38 ng/ml and 51 pmol/min/mg protein). There was a strong positive correlation (rs=0.75, P<0.0005) between the plasma levels of 7-DHC and the activities of hepatic HMG-CoA reductase in these patients. This correlation was further improved when the plasma levels of 7-DHC were expressed relative to those of cholesterol (rs=0.90, P<0.0001). The results show that the level of 7-DHC in plasma reflects the activity of HMG-CoA reductase in the liver.

血浆中7-脱氢胆固醇的水平反映了肝脏中3-羟基-3-甲基戊二酰辅酶A还原酶的活性
对胆囊切除术患者肝活检中胆固醇前体7-脱氢胆固醇(7-DHC)血浆水平与胆固醇生物合成限速酶、3-羟基-3-甲基戊二酰辅酶A (HMG-CoA)还原酶活性进行了比较。一些患者在手术前用胆胺、去氧胆酸或鹅去氧胆酸治疗,以改变酶的活性。未处理组7-DHC和HMG-CoA还原酶活性的中位数分别为55 ng/ml和98 pmol/min/mg蛋白。胆胺组(85 ng/ml和439 pmol/min/mg蛋白)和去氧胆酸组(86 ng/ml和173 pmol/min/mg蛋白)患者的胆固醇水平和酶活性升高,鹅去氧胆酸组(38 ng/ml和51 pmol/min/mg蛋白)患者的胆固醇水平和酶活性降低。这些患者血浆7-DHC水平与肝脏HMG-CoA还原酶活性呈正相关(rs=0.75, P<0.0005)。当血浆7-DHC水平相对于胆固醇水平表达时,这种相关性进一步得到改善(rs=0.90, P<0.0001)。结果表明,血浆7-DHC水平反映肝脏HMG-CoA还原酶活性。
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