共价抑制剂四氢脂抑素在体外对胰脂肪酶的抑制作用。
Inhibition of pancreatic lipase in vitro by the covalent inhibitor tetrahydrolipstatin.
作者信息
Hadváry P, Lengsfeld H, Wolfer H
机构信息
F. Hoffmann-La Roche & Co., Ltd., Pharmaceutical Research Department, Basel, Switzerland.
出版信息
Biochem J. 1988 Dec 1;256(2):357-61. doi: 10.1042/bj2560357.
Abstract
Tetrahydrolipstatin inhibits pancreatic lipase from several species, including man, with comparable potency. The lipase is progressively inactivated through the formation of a long-lived covalent intermediate, probably with a 1:1 stoichiometry. The lipase substrate triolein and also a boronic acid derivative, which is presumed to be a transition-state-form inhibitor, retard the rate of inactivation. Therefore, in all probability, tetrahydrolipstatin reacts with pancreatic lipase at, or near, the substrate binding or active site. Tetrahydrolipstatin is a selective inhibitor of lipase; other hydrolases tested were at least a thousand times less potently inhibited.
摘要
四氢脂抑素能抑制包括人类在内的多种物种的胰脂肪酶，其效力相当。脂肪酶通过形成一种可能具有1:1化学计量比的长寿命共价中间体而逐渐失活。脂肪酶底物三油酸甘油酯以及一种被认为是过渡态形式抑制剂的硼酸衍生物会延缓失活速率。因此，很可能四氢脂抑素在底物结合位点或活性位点处或其附近与胰脂肪酶发生反应。四氢脂抑素是一种脂肪酶的选择性抑制剂；所测试的其他水解酶受到的抑制效力至少低一千倍。
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本文引用的文献
1
[ON THE DETERMINATION OF TRYPSIN AND CHYMOTRYPSIN WITH AMINO-P-NITROANILIDES].[关于用对硝基苯胺测定胰蛋白酶和糜蛋白酶]
Hoppe Seylers Z Physiol Chem. 1965;340:1-10. doi: 10.1515/bchm2.1965.340.1-2.1.
2
Esters of methanesulfonic acid as irreversible inhibitors of acetylcholinesterase.甲磺酸酯作为乙酰胆碱酯酶的不可逆抑制剂
J Biol Chem. 1962 Oct;237:3245-9.
3
The preparation and properties of two new chromogenic substrates of trypsin.两种新型胰蛋白酶显色底物的制备与性质
Arch Biochem Biophys. 1961 Nov;95:271-8. doi: 10.1016/0003-9861(61)90145-x.
4
A rapid method of total lipid extraction and purification.一种快速的总脂质提取与纯化方法。
Can J Biochem Physiol. 1959 Aug;37(8):911-7. doi: 10.1139/o59-099.
5
Boronic acid inhibitors of porcine pancreatic lipase.猪胰脂肪酶的硼酸抑制剂
J Biol Chem. 1980 Jun 10;255(11):5064-8.
6
An improved synthesis of 1,2-dialkyl glycerol ethers and the synthesis of 14C-labelled trialkyl glycerol ethers.1,2 - 二烷基甘油醚的改进合成方法及14C标记的三烷基甘油醚的合成
Chem Phys Lipids. 1968 Jun;2(2):168-72. doi: 10.1016/0009-3084(68)90020-0.
7
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J Antibiot (Tokyo). 1987 Aug;40(8):1086-91. doi: 10.7164/antibiotics.40.1086.
8
Lipstatin, an inhibitor of pancreatic lipase, produced by Streptomyces toxytricini. I. Producing organism, fermentation, isolation and biological activity.利普司他汀，一种由产毒链霉菌产生的胰脂肪酶抑制剂。I. 产生菌、发酵、分离及生物活性。
J Antibiot (Tokyo). 1987 Aug;40(8):1081-5. doi: 10.7164/antibiotics.40.1081.
9
10
Isolation and properties of the mixed lipid micelles present in intestinal content during fat digestion in man.人体脂肪消化过程中肠道内容物中混合脂质微团的分离与特性
J Clin Invest. 1975 Oct;56(4):781-91. doi: 10.1172/JCI108156.
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