CYCLIC-AMP AND THE REGULATION OF CHOLESTEROL-METABOLISM
CYCLIC-AMP AND THE REGULATION OF CHOLESTEROL-METABOLISM
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DOI：
10.1042/bst0200454
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发表时间：
1992-05-01
影响因子：
3.9
通讯作者：
BOTHAM, KM
中科院分区：
文献类型：
--
作者：
BOTHAM, KM
环AMP或多或少地参与调节相互作用以调节细胞内胆固醇代谢的四种关键酶：HMG CoA还原酶、ACAT、胆固醇酯水解酶和胆固醇7 α羟化酶。这些酶与目前证据表明可能涉及环AMP的位点之间的关系总结在图3中。胆固醇7 α羟化酶控制胆固醇在肝脏中转化为胆汁酸，从而通过胆汁将其从体内清除，但在肝外组织中的胆固醇代谢中不起主要作用。很明显，环腺苷酸是能够影响这种酶的活性在肝亚细胞组分和离体肝细胞在体外，在我们的实验室的研究表明，在细胞内的Ca2+流量的变化可能是重要的，在其作用机制。然而，环核苷酸是否具有调节体内胆固醇7 α羟化酶活性的作用尚不清楚。HMG CoA还原酶在体外和体内均被磷酸化灭活，但尽管环AMP和胰高血糖素已被证明可抑制该酶，但环AMP依赖性蛋白激酶并不直接参与。环核苷酸影响该系统的确切机制尚不清楚，但可能与微粒体磷酸酶的激活有关。ACAT的活性已被证明在体外许多组织中通过磷酸化调节，但环AMP的参与尚未得到明确证明。（250字处删节）
Cyclic AMP has been implicated to a greater or lesser extent in the regulation of four key enzymes which interact to regulate intracellular cholesterol metabolism; HMG CoA reductase; ACAT; cholesteryl ester hydrolase; and cholesterol 7 alpha hydroxylase. The relationship between these enzymes and the sites where current evidence suggests that cyclic AMP may be involved are summarized in Fig. 3. Cholesterol 7 alpha hydroxylase controls the catabolism of cholesterol to bile acids in the liver, and thus its removal from the body via the bile, but does not have a major role in cholesterol metabolism in extrahepatic tissues. It is clear that cyclic AMP is able to influence the activity of this enzyme in liver sub-cellular fractions and isolated hepatocytes in vitro, and studies in our laboratory have shown that changes in Ca2+ fluxes within the cell may be important in its mechanism of action. Whether or not the cyclic nucleotide has a role regulating cholesterol 7 alpha hydroxylase activity in vivo, however, is not known. HMG CoA reductase is inactivated by phosphorylation both in vitro and in vivo, but although cyclic AMP and glucagon have been shown to inhibit the enzyme, cyclic AMP-dependent protein kinase is not directly involved. The exact mechanism by which the cyclic nucleotide influences the system remains unclear, but it may be related to activation of microsomal phosphatases. The activity of ACAT has been shown to be modulated by phosphorylation in a number of tissues in vitro, but the involvement of cyclic AMP has not been unequivocally demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)