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SHR Neuro Cancer Cardio Lipid Metab Microb

Eichmann, TO; Kumari, M; Haas, JT; Farese, RV; Zimmermann, R; Lass, A; Zechner, R.
Studies on the substrate and stereo/regioselectivity of adipose triglyceride lipase, hormone-sensitive lipase, and diacylglycerol-O-acyltransferases.
J Biol Chem. 2012; 287(49): 41446-57. Doi: 10.1074/jbc.M112.400416 [OPEN ACCESS]
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Leading authors Med Uni Graz: Eichmann Thomas
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Abstract:: Adipose triglyceride lipase (ATGL) is rate-limiting for the initial step of triacylglycerol (TAG) hydrolysis, generating diacylglycerol (DAG) and fatty acids. DAG exists in three stereochemical isoforms. Here we show that ATGL exhibits a strong preference for the hydrolysis of long-chain fatty acid esters at the sn-2 position of the glycerol backbone. The selectivity of ATGL broadens to the sn-1 position upon stimulation of the enzyme by its co-activator CGI-58. sn-1,3 DAG is the preferred substrate for the consecutive hydrolysis by hormone-sensitive lipase. Interestingly, diacylglycerol-O-acyltransferase 2, present at the endoplasmic reticulum and on lipid droplets, preferentially esterifies sn-1,3 DAG. This suggests that ATGL and diacylglycerol-O-acyltransferase 2 act coordinately in the hydrolysis/re-esterification cycle of TAGs on lipid droplets. Because ATGL preferentially generates sn-1,3 and sn-2,3, it suggests that TAG-derived DAG cannot directly enter phospholipid synthesis or activate protein kinase C without prior isomerization.
Find related publications in this database (using NLM MeSH Indexing): Adipose Tissue - enzymology; Animals - administration & dosage; COS Cells - administration & dosage; Chlorocebus aethiops - administration & dosage; Cloning, Molecular - administration & dosage; Diacylglycerol O-Acyltransferase - metabolism; Glutathione Transferase - metabolism; Lipase - metabolism; Lipolysis - administration & dosage; Male - administration & dosage; Mice - administration & dosage; Mice, Inbred C57BL - administration & dosage; Models, Chemical - administration & dosage; Protein Isoforms - administration & dosage; Protein Kinase C - metabolism; Signal Transduction - administration & dosage; Stereoisomerism - administration & dosage; Sterol Esterase - metabolism; Type C Phospholipases - chemistry