Linked Life Data

2161255

Source:http://linkedlifedata.com/resource/pubmed/id/2161255

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1990-7-12
pubmed:abstractText
(Rp)- and (Sp)-1,2-dipalmitoyl-sn-glycero-3-thiophosphoinositol (DPPsI) were synthesized as a mixture and their configurations assigned on the basis of the stereospecific hydrolysis catalyzed by phospholipase A2 (PLA2) from bee venom. PLA2 is known to be stereospecific to the Rp isomer of 1,2-dipalmitoyl-sn-glycero-3-thiophosphocholine (DPPsC) and 1,2-dipalmitoyl-sn-glycero-3-thiophosphoethanolamine (DPPsE). Since the configurations of (Rp)- and (Sp)-DPPsI correspond to those of (Sp)- and (Rp)-DPPsC, respectively, due to a change in priority, the isomer specifically hydrolyzed by PLA2 was assigned to (Sp)-DPPsI. The DPPsI analogues were then used to probe the mechanism and to elucidate the steric course of the reaction catalyzed by phosphatidylinositide-specific phospholipase C (PI-PLC) from Bacillus cereus and for both isozyme I and isozyme II of PI-PLC from guinea pig uterus. It was found that the Rp isomer of DPPsI is the preferred substrate for all three PI-PLCs. Thus PI-PLC shows the same stereospecificity as phosphatidylcholine-specific PLC (PC-PLC), which prefers the Sp isomer of DPPsC. The ratio of the two products inositol 1,2-cyclic phosphorothioate (cIPs) and inositol phosphorothioate (IPs) was not significantly perturbed by the use of phosphorothioate analogue for all three PI-PLCs, which implies that IPs is not produced by enzyme-mediated ring opening of cIPs and supports a parallel pathway for the formation of both products. In order to elucidate the steric course of the cyclization reaction, exo and endo isomers of cIPs were synthesized and their absolute configurations at phosphorus were determined by nuclear magnetic resonance and other techniques. It was found that exo-cIPs is the product produced by all three PI-PLCs. Thus the steric course of the conversion DPPsI to cIPs catalyzed by all three PI-PLCs was inversion of configuration at phosphorus. These results taken together suggest that the reaction catalyzed by PI-PLC most likely proceeds via direct attack by the 2-OH group to generate the cyclic product, and parallelly by water to generate the noncyclic inositol phosphates, without involving a covalent enzyme-phosphoinositol intermediate.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2747-57
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Phospholipids chiral at phosphorus. Stereochemical mechanism of reactions catalyzed by phosphatidylinositide-specific phospholipase C from Bacillus cereus and guinea pig uterus.
pubmed:affiliation
Department of Chemistry, Ohio State University, Columbus 43210.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't