title: Coenzyme A-dependent, ATP-independent acylation of 2-acyl lysophosphatidylinositol in rat liver microsomes.
abstract: Phosphatidylinositol (PI) is synthesized from cytidine-diphosphodiacylglycerol (CDP-DAG) and inositol by the enzyme PI synthase. CDP-DAG is itself synthesized from phosphatidic acid and CTP. The observation that PI differs in fatty acid composition from its precursors CDP-DAG and phosphatidic acid led to the proposal that following its synthesis the fatty acids of PI are removed and replaced by others in a process called fatty acid remodelling. Previously, we used rat liver microsomes to study the molecular mechanisms of PI remodelling. Following its synthesis, PI is rapidly deacylated to form lysoPI which is reacylated to form new PI species. PI remodelling occurs predominantly at the 1-position. We demonstrate here that lysoPI can be acylated in the 1-position in an ATP-independent manner. The acylation of 2-acyl lysoPI by the coenzyme A-dependent, ATP-independent mechanism was examined. The acylation exhibits a pH optimum of 7.5, does not require a divalent cation, and is not inhibited by Ca2+ or Mg2+, although Zn2+ is a potent inhibitor. The apparent Km values for coenzyme A and 2-acyl lysoPI are 14 microM and 30 microM, respectively. The acylation of 2-acyl lysoPI incorporates primarily stearic acid into the 1-position of PI, as would be expected based on the fatty acid composition of steady-state PI in rat hepatocytes.
authors.affiliation: Laboratory of Molecular Oncology, Rockefeller University, New York.
authors.forename: J C
authors.initials: JC
authors.lastname: Darnell
authors.forename: A R
authors.initials: AR
authors.lastname: Saltiel
mesh_terms: D000215:Acylation; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D003065:Coenzyme A / Q000502:physiology*; D008246:Lysophospholipids / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D008246:Lysophospholipids; C025449:lysophosphatidylinositol; D000255:Adenosine Triphosphate; D003065:Coenzyme A