Distinct properties of the two isoforms of CDP-diacylglycerol synthase.
CDP-diacylglycerol synthases (CDS) are critical enzymes that catalyze the formation of CDP-diacylglycerol (CDP-DAG) from phosphatidic acid (PA). Here we show in vitro that the two isoforms of human CDS, CDS1 and CDS2, show different acyl chain specificities for its lipid substrate. CDS2 is selective for the acyl chains at the sn-1 and sn-2 positions, the most preferred species being 1-stearoyl-2-arachidonoyl-sn-phosphatidic acid. CDS1, conversely, shows no particular substrate specificity, displaying similar activities for almost all substrates tested. Additionally, we show that inhibition of CDS2 by phosphatidylinositol is also acyl chain-dependent, with the strongest inhibition seen with the 1-stearoyl-2-arachidonoyl species. CDS1 shows no acyl chain-dependent inhibition. Both CDS1 and CDS2 are inhibited by their anionic phospholipid end products, with phosphatidylinositol-(4,5)-bisphosphate showing the strongest inhibition. Our results indicate that CDS1 and CDS2 could create different CDP-DAG pools that may serve to enrich different phospholipid species with specific acyl chains.
Department of Biochemistry and Biomedical Sciences, McMaster University , Hamilton, Ontario L8N 3Z5, Canada.
Kenneth
K
D'Souza
Yeun Ju
YJ
Kim
Tamas
T
Balla
Richard M
RM
Epand
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003567:Cytidine Diphosphate Diglycerides / Q000378:metabolism; D002798:Diacylglycerol Cholinephosphotransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D010712:Phosphatidic Acids / Q000737:chemistry / Q000378:metabolism; D010716:Phosphatidylinositols / Q000494:pharmacology; D021381:Protein Transport; D013379:Substrate Specificity
D003567:Cytidine Diphosphate Diglycerides; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D010712:Phosphatidic Acids; D010716:Phosphatidylinositols; D002798:Diacylglycerol Cholinephosphotransferase