[HTML][HTML] Studies on the substrate and stereo/regioselectivity of adipose triglyceride lipase, hormone-sensitive lipase, and diacylglycerol-O-acyltransferases

TO Eichmann, M Kumari, JT Haas, RV Farese Jr… - Journal of Biological …, 2012 - Elsevier
TO Eichmann, M Kumari, JT Haas, RV Farese Jr, R Zimmermann, A Lass, R Zechner
Journal of Biological Chemistry, 2012Elsevier
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 …
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.
Elsevier