title: Differential metabolism of diradyl glycerol molecular subclasses and molecular species by rabbit brain diglyceride kinase.
abstract: Elevations in the mass of ether-linked diglycerides (i.e. 1-O-alk-1'-enyl-2-acyl-sn-glycerol (AAG) and 1-O-alkyl-2-acyl-sn-glycerol (Alkyl AG)) during cellular activation are prolonged in comparison to their 1,2-diacyl-sn-glycerol (DAG) counterparts. Since the metabolic removal of DAG is determined, in large part, by the rate of its phosphorylation by diglyceride kinase, we quantified differences in the activity of diglyceride kinase utilizing individual subclasses of diradyl glycerols as substrate. Rabbit brain microsomal diglyceride kinase activity was over 30-fold greater utilizing DAG as substrate (25.8 nmol.mg-1.min-1) in comparison to AAG (0.8 nmol.mg-1.min-1). No alterations in the affinity of microsomal diglyceride kinase for ATP were present (Km approximately 0.5 mM) utilizing each diradyl glycerol subclass. Similar subclass specificities for diglyceride kinase (i.e. DAG greater than Alkyl AG much greater than AAG) were present in brain and liver cytosol as well as in liver microsomes utilizing multiple assay conditions. In sharp contrast, Escherichia coli diglyceride kinase phosphorylated DAG, Alkyl AG, or AAG diradyl glycerol molecular subclasses at identical rates. Furthermore, although DAG was rapidly hydrolyzed by diglyceride lipase, catabolism of AAG or Alkyl AG by plasmalogenase, alkyl ether hydrolase, or diglyceride/monoglyceride lipase was undetectable. Collectively, these results demonstrate the importance of the differential catabolism of each diradyl glycerol molecular subclass as a primary determinant of their biologic half-lives. Since individual subclasses of diglycerides have distinct physical properties and physiologic functions, these results underscore the importance of lipid subclass specific metabolism in tailoring individual cellular responses during activation.
authors.affiliation: Division of Molecular and Cellular Cardiovascular Biochemistry, Washington University, St. Louis, Missouri 63110.
authors.forename: D A
authors.initials: DA
authors.lastname: Ford
authors.forename: R W
authors.initials: RW
authors.lastname: Gross
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology*; D003600:Cytosol / Q000201:enzymology; D003902:Detergents; D002798:Diacylglycerol Cholinephosphotransferase / Q000378:metabolism; D019852:Diacylglycerol Kinase; D004075:Diglycerides / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology; D004982:Ethanolaminephosphotransferase / Q000378:metabolism; D004987:Ethers; D005989:Glycerides / Q000378:metabolism*; D008049:Lipase / Q000378:metabolism; D008823:Micelles; D008861:Microsomes / Q000201:enzymology; D008862:Microsomes, Liver / Q000378:metabolism; D010770:Phosphotransferases / Q000378:metabolism*; D011817:Rabbits; D013379:Substrate Specificity
chemical_list: D003902:Detergents; D004075:Diglycerides; D004987:Ethers; D005989:Glycerides; D008823:Micelles; D010770:Phosphotransferases; D019852:Diacylglycerol Kinase; D004982:Ethanolaminephosphotransferase; D002798:Diacylglycerol Cholinephosphotransferase; D008049:Lipase