Inhibition of diacylglycerol acyltransferase by betulinic acid from Alnus hirsuta
Inhibition of diacylglycerol acyltransferase by betulinic acid from Alnus hirsuta
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DOI：
10.1055/s-2005-916178
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发表时间：
2006-02-01
期刊：
影响因子：
2.7
通讯作者：
Kim, YK
中科院分区：
文献类型：
--
作者：
Chung, MY;Rho, MC;Kim, YK
在筛选天然产物二酰基甘油酰基转移酶（DGAT）抑制剂的过程中，从毛毛桤木甲醇提取物中分离到羽桃烷型三萜白桦酸。它能有效抑制大鼠肝微粒体中的DGAT， IC50值为9.6 μ M。酶动力学研究表明，以[C-14]油酰coa为底物，表观Km和Ki值分别为13.3 μ M和8.1 μ M。白桦酸降低了表观Vmax，而表观Km保持不变。因此，白桦酸对DGAT抑制的Lineweaver-Burk图显示为非竞争性抑制。在基于细胞的实验中，白桦酸抑制人HepG2细胞生成甘油三酯（TG）。这些发现表明，白桦酸可能是治疗肥胖的潜在先导化合物。
During the screening for diacylglycerol acyltransferase (DGAT) inhibitors from natural products, the lupane-type triterpenoid betulinic acid was isolated from the methanol extract of Alnus hirsuta. It potently inhibited DGAT in the rat liver microsomes with an IC50 value of 9.6 mu M. Enzyme kinetic Studies showed apparent Km and Ki values of 13.3 mu M and 8.1 mu M using [C-14]oleoyl-CoA as a Substrate. A decrease in the apparent Vmax was observed with betulinic acid, whereas the apparent Km remained constant. Therefore, a Lineweaver-Burk plot of DGAT inhibition by betulinic acid showed a non-competitive type of inhibition. In the cell-based assay, betulinic acid inhibited triglyceride (TG) formation by human HepG2 cells. These findings suggest that betulinic acid may be a potential lead Compound in the treatment of obesity.