Linked Life Data

11724615

Source:http://linkedlifedata.com/resource/pubmed/id/11724615

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
48
pubmed:dateCreated
2001-11-28
pubmed:abstractText
The mechanism of orotidine 5'-monophosphate decarboxylase was studied computationally by using the decarboxylation of orotic acid analogues as model systems. These calculations indicate that mechanisms involving proton transfer to the 2-oxygen or the 4-oxygen are energetically favorable, as compared to direct decarboxylation without proton transfer, for a series of model compounds where N1 is substituted with respectively H, CH(3), and a tetrahydrofuran moiety. Proton transfer to the 4-oxygen during decarboxylation is found to be energetically more favorable than 2-protonation, which is attributable to both the 4-oxygen site being more basic and an apparent intrinsic preference for the 4-protonation pathway. (15)N isotope effect calculations were also conducted, and compared to experimental (15)N isotope effects previously measured at N1 by Rishavy and Cleland (Biochemistry 2000, 39, 4569-4574). The theoretical isotope effects establish, for the first time, that the experimental (15)N isotope effect is consistent with decarboxylation without protonation, as well as with decarboxylation with protonation, at either O2 or at O4. Furthermore, we propose herein an isotope measurement that could potentially distinguish among mechanisms involving protonation from those that do not involve proton transfer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0002-7863
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
123
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
12067-73
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Theoretical studies of mechanisms and kinetic isotope effects on the decarboxylation of orotic acid and derivatives.
pubmed:affiliation
Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey 08854, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't