Differential Inhibition of HMG-CoA Synthase and Pancreatic Lipase by the Specific Chiral Isomers of 
-Lactone DU-6622
Authors: Tomoda H.1; Ohbayashi N.1; Kumagai H.1; Hashizume H.2; Sunazuka T.1; 
mura S.1
Source: Biochemical and Biophysical Research Communications, Volume 265, Number 2, November 1999 , pp. 536-540(5)
Publisher: Academic Press
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Abstract:
A synthetic -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)--lactones) was found to inhibit HMG-CoA synthase (IC50: 0.15 
M) and pancreatic lipase (IC50: 120 M). 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 (IC50: 0.098 M vs 270 M for pancreatic lipase), while the (2S, 3S)-isomer markedly increased the specificity of lipase inhibition (IC50: 27 M vs 31 M for HMG-CoA synthase). Furthermore, the (2R, 3R)-isomer strongly inhibited the binding of [14C]hymeglusin to HMG-CoA synthase, indicating that the isomer was bound to the same site of the synthase as hymeglusin. The (2R, 3R)--lactone is responsible for the specific inhibition of HMG-CoA synthase, while the (2S, 3S)--lactone is responsible for the inhibition of pancreatic lipase. Copyright 1999 Academic Press.
Language: English
Document Type: Research article
Affiliations: 1: Research Center for Biological Function, Kitasato Institute, Minato-ku, Tokyo, 108-8642, Japan 2: Fuji Chemical Industries Co., Takaoka, Toyama, Japan
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