Linked Life Data

14973367

Source:http://linkedlifedata.com/resource/pubmed/id/14973367

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-2-19
pubmed:abstractText
A series of inhibitors of glucosylceramide synthesis, the PDMP based family of compounds, has been developed as a tool for the study of sphingolipid biochemistry and biology. During the course of developing more active glucosylceramide synthase inhibitors, we identified a second site of inhibitory activity for PDMP and its structural homologues that accounted for the ability of the inhibitors to raise cell and tissue ceramide levels. This inhibitory activity was directed against a previously unknown pathway for ceramide metabolism, viz. the formation of 1- O -acylceramide. In this pathway the addition of a fatty acyl group to the primary hydroxyl of ceramide occurs through a transacylation with either phosphatidylethanolamine or phosphatidylcholine as a substrate. However, both in the absence and presence of ceramide, water serves as an acceptor for the fatty acid. Thus the enzyme may be considered to be a phospholipase A2. The enzyme is unique in that it has an acidic pH optimum and is localized to lysosomes by cell fractionation. More recently, the 1- O -acylceramide synthase has been purified, sequenced, and cloned. This phospholipase A2 was discovered to be structurally homologous to lecithin cholesterol acyltransferase (LCAT). However, this phospholipase A2 does not recognize cholesterol and lacks the defined lipoprotein-binding domain present in LCAT. We now refer to this enzyme as lysosomal phospholipase A2 (LPLA2). Although acidic phospholipase A2 activities have been previously identified, LPLA2 appears to be the first lysosomal PLA2 to have been sequenced. This new phospholipase A2 lacks an obvious and proven biological function.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Acyltransferases, http://linkedlifedata.com/resource/pubmed/chemical/Ceramides, http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Glucosyltransferases, http://linkedlifedata.com/resource/pubmed/chemical/Morpholines, http://linkedlifedata.com/resource/pubmed/chemical/N-acetylsphingosine, http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A, http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A2, http://linkedlifedata.com/resource/pubmed/chemical/RV 538, http://linkedlifedata.com/resource/pubmed/chemical/Sphingosine, http://linkedlifedata.com/resource/pubmed/chemical/ceramide glucosyltransferase, http://linkedlifedata.com/resource/pubmed/chemical/phospholipase A2, group XV
pubmed:status
MEDLINE
pubmed:issn
0282-0080
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
25-32
pubmed:dateRevised
2010-10-8
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
A turn in the road: How studies on the pharmacology of glucosylceramide synthase inhibitors led to the identification of a lysosomal phospholipase A2 with ceramide transacylase activity.
pubmed:affiliation
Division of Nephrology, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109, USA. jshayman@umich.edu
pubmed:publicationType
Journal Article, Review