Diacylglycerol acyltransferase inhibition

Mectianism of Action A combination of ethyl esters of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that inhibits acyl coenzyme A l,2-diacylglycerol acyltransferase and increases peroxisomal oxidation in the liver. Therapeutic Effect Reduces the synthesis of triglycerides in the liver. 

N Mayorek, J Bar-Tana. Inhibition of diacylglycerol acyltransferase by 2-bromo-octanoate in cultured rat hepatocytes. J Biol Chem 260 6528-6532, 1985. 

Casaschi, A., Wang, Q., Dang, K., Richards, A., Theriault, A. (2002). Intestinal apoUpoprotein B secretion is inhibited by the flavonoid quercetin potential role of microsomal triglyceride transfer protein and diacylglycerol acyltransferase. Lipids, 37, 647-652. 

Chemicals known to inhibit phosphatidic acid phosphatase (25 mM EDTA) and diacylglycerol acyltransferase (5 mM DIPFP, 1.5 mM 2-BrOA) decreased the rate of incorporation of C-erucoyl-CoA into triacylglycerols by 85%, 60% and 84%, respectively, but this inhibition was not accompanied by an accumulation of C-erucoyl moieties in LPA, PA or DAG, or in other polar lipids [108]. 

Photoreactive acyl-CoA analogs were used in the characterization of diacylglycerol acyltransferase (DGAT, EC 2.3.1.20) from microspore-derived (MD) embryos of oilseed rape. 12-[(4-Azidosalicyl)amino]dodecanoyl-CoA (ASD-CoA) was more effective than 12-azidooleoyl-CoA in the inhibition of DGAT activity. Photoaffinity labeling of particulate and solubilized fractions with 25l-labeled ASD-CoA resulted in the incoiporation of label into a number of polypeptides but fewer polypeptides were labeled in the solubilized fraction. Thus, photoaffinity labeling may be useful in the purification and characterization of DGAT. 

Isochromophilones VII (190) and VIII (191) from a Penicillium sp. inhibit diacylglycerol acytransferase activity with IC5o values of 20.0 and 127 pM and acyl-CoA cholesterol acyltransferase activity with IC50 values of 24.5 and 47.0, respectively. They also show moderate antimicrobial activity [153]. 

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