Linked Life Data

1845995

Source:http://linkedlifedata.com/resource/pubmed/id/1845995

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1991-2-12
pubmed:abstractText
Glycerophosphoinositol (GroPIns) is a major inositol phosphate in many cell types. In this study we have determined the optimal conditions (pH 8.0 and 0.5 mM MnCl2) for the metabolism of this molecule in an extract from human placenta, and we show that the major product is inositol (1)-phosphate (Ins(1)P). The enzyme activity that catalyzes this reaction is contained in the same protein designated previously as inositol-(1,2)-cyclic-phosphate 2-inositolphosphohydrolase (cyclic hydrolase), a phosphodiesterase that catalyzes the conversion of inositol-(1,2)-cyclic phosphate (cIns(1,2)P) to Ins(1)P. In addition, the enzyme also catalyzes the production of Ins(1)P from inositol (1)-methylphosphate. All of these substrates, (cIns(1,2)P, GroPIns, and inositol (1)-methylphosphate), contain a phosphodiester bond at the 1-position of the inositol ring. Additional phosphate groups on the 4- or 5-positions of the inositol ring prevent hydrolysis by cyclic hydrolase. The Km of the enzyme for GroPIns is 0.67 mM, and the Vm is 5 mumol/min/mg of protein. GroPIns competitively inhibits cIns(1,2)P hydrolysis with a Ki equal to its Km as a substrate. Hydrolysis of GroPIns and cIns(1,2)P is stimulated by MnCl2, phosphatidylserine, and [ethylenebis(oxyethylenenitrilo)]tetraacetic acid (EGTA). However, whereas cIns(1,2)P hydrolysis is increased 5-8-fold by phosphatidylserine and EGTA only a 2-fold increase of GroPIns hydrolysis occurs under the same conditions. Hydrolysis of both GroPIns and cIns(1,2)P is inhibited by Ins(2)P; the ID50 values are 12 and 1 microM, respectively. There are significant quantities of GroPIns and Ins(2)P in 3T3 cells, indicating that these compounds that alter cIns(1,2)P hydrolase activity may modulate intracellular levels of cIns(1,2)P. Finally, we present evidence suggesting that the substrate specificity of this enzyme is altered during cell transformation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
266
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
851-6
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:1845995-Animals, pubmed-meshheading:1845995-Annexin A3, pubmed-meshheading:1845995-Chelating Agents, pubmed-meshheading:1845995-Chlorides, pubmed-meshheading:1845995-Chromatography, DEAE-Cellulose, pubmed-meshheading:1845995-Enzyme Activation, pubmed-meshheading:1845995-Female, pubmed-meshheading:1845995-Humans, pubmed-meshheading:1845995-Hydrolysis, pubmed-meshheading:1845995-Inositol Phosphates, pubmed-meshheading:1845995-Manganese, pubmed-meshheading:1845995-Manganese Compounds, pubmed-meshheading:1845995-Mice, pubmed-meshheading:1845995-Phosphatidylinositols, pubmed-meshheading:1845995-Phospholipids, pubmed-meshheading:1845995-Phosphoric Diester Hydrolases, pubmed-meshheading:1845995-Placenta, pubmed-meshheading:1845995-Pregnancy, pubmed-meshheading:1845995-Substrate Specificity
pubmed:year
1991
pubmed:articleTitle
Inositol-1,2-cyclic-phosphate 2-inositolphosphohydrolase. Substrate specificity and regulation of activity by phospholipids, metal ion chelators, and inositol 2-phosphate.
pubmed:affiliation
Division of Hematology-Oncology, Washington University School of Medicine, St. Louis, Missouri 63110.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't