Differential inhibition of HMG-CoA synthase and pancreatic lipase by the specific chiral isomers of beta-lactone DU-6622.
Differential inhibition of HMG-CoA synthase and pancreatic lipase by the specific chiral isomers of beta-lactone DU-6622.
复制标题
β-内酯 DU-6622 的特定手性异构体对 HMG-CoA 合酶和胰脂肪酶的差异抑制。
DOI：
10.1006/bbrc.1999.1712
复制
发表时间：
1999
影响因子：
3.1
通讯作者：
S. Ōmura
中科院分区：
文献类型：
--
作者：
H. Tomoda;Naomi Ohbayashi;H. Kumagai;H. Hashizume;T. Sunazuka;S. Ōmura
A synthetic beta-lactone trans-DU-6622 (3-hydroxy-2-(hydroxymethyl)-5-[7-(methylcarbonyl)-naphthalen++ +-1-yl]pentanoic acid 1,3-lactone, a mixture of (2R, 3R)- and (2S, 3S)-beta-lactones) was found to inhibit HMG-CoA synthase (IC(50): 0. 15 microM) and pancreatic lipase (IC(50): 120 microM). The effects of the optically pure DU-6622 isomers on the two enzymes were compared. The (2R, 3R)-isomer was shown to be a highly specific inhibitor of HMG-CoA synthase (IC(50): 0.098 microM vs 270 microM for pancreatic lipase), while the (2S, 3S)-isomer markedly increased the specificity of lipase inhibition (IC(50): 27 microM vs 31 microM for HMG-CoA synthase). Furthermore, the (2R, 3R)-isomer strongly inhibited the binding of [(14)C]hymeglusin to HMG-CoA synthase, indicating that the isomer was bound to the same site of the synthase as hymeglusin. The (2R, 3R)-beta-lactone is responsible for the specific inhibition of HMG-CoA synthase, while the (2S, 3S)-beta-lactone is responsible for the inhibition of pancreatic lipase.
大鼠肝脏 3-羟基-3-甲基戊二酰辅酶 A 合酶的调节和人类基因的染色体定位。
DOI：
--
发表时间：
1986
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Mehrabian,M;Callaway,KA;Clarke,CF;Tanaka,RD;Greenspan,M;Lusis,AJ;Sparkes,RS;Mohandas,T;Edmond,J;Fogelman,AM
通讯作者：
Fogelman,AM