Ahlberg J, Angelin B, Björkhem I, Einarsson K, Leijd B
J Lipid Res. 1979 Jan;20(1):107-15.
In vivo studies have shown abnormalities in cholesterol and bile acid metabolism in primary hyperlipoproteinemia (HLP). The aim of the present investigation was to determine if the increased production of cholesterol in HLP type IV can be attributed to a correspondingly high level of the hepatic 3-hydroxy-3-methylglutaryl (HMG) CoA reductase activity and if the low cholic acid: chenodeoxycholic acid synthesis ratio in HLP type II is due to some hydroxylase deficiency. Liver biopsies from 26 normolipidemic and 25 hyperlipidemic (10 type IIa, 6 type IIb, and 9 type IV) patients undergoing elective cholecystectomy were assayed for HMG CoA reductase activity, 12 alpha-hydroxylase activity, and 25-hydroxylase activity. The HMG CoA reductase activity was normal in HLP type IIa and type IIb and was increased about twice HLP type IV (P less than 0.001). The 12 alpha- and 25-hydroxylase activities were normal in all groups of patients. The results are compatible with a normal cholesterol synthesis in the liver in HLP type II. A reduced 12 alpha- or 25-hydroxylase activity cannot explain the low production of cholic acid relative to chenodeoxycholic acid in this type of HLP. The elevated HMG CoA reductase activity found in the liver of type IV patients may, however, be part of the explanation for the elevated synthesis of cholesterol often seen in these patients.
体内研究表明，原发性高脂蛋白血症（HLP）患者存在胆固醇和胆汁酸代谢异常。本研究的目的是确定IV型HLP患者胆固醇生成增加是否可归因于肝脏3-羟基-3-甲基戊二酰辅酶A（HMG）还原酶活性相应升高，以及II型HLP患者胆酸：鹅去氧胆酸合成比例降低是否是由于某种羟化酶缺乏所致。对26名血脂正常和25名高脂血症（10名IIa型、6名IIb型和9名IV型）接受择期胆囊切除术患者的肝脏活检组织进行HMG辅酶A还原酶活性、12α-羟化酶活性和25-羟化酶活性检测。IIa型和IIb型HLP患者的HMG辅酶A还原酶活性正常，IV型HLP患者的该活性升高约两倍（P<0.001）。所有患者组的12α-和25-羟化酶活性均正常。结果表明II型HLP患者肝脏中的胆固醇合成正常。12α-或25-羟化酶活性降低不能解释此类HLP中胆酸相对于鹅去氧胆酸生成减少的现象。然而，IV型患者肝脏中发现的HMG辅酶A还原酶活性升高可能是这些患者中常见的胆固醇合成增加的部分原因。
