Linked Life Data

3997815

Source:http://linkedlifedata.com/resource/pubmed/id/3997815

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1985-6-27
pubmed:abstractText
Metabolites of 5-amino-4-imidazolecarboxamide riboside (Z-riboside) have potential roles in the regulation of cellular metabolism and as pharmacological agents in several pathological situations. Before studying Z-riboside metabolism it was necessary to develop methods for identifying and quantitating 5(4)-amino-4(5)-imidazolecarboxamide metabolites. These studies utilized Chinese hamster ovary fibroblast auxotrophic mutants to identify and isolate compounds relevant to Z-riboside metabolism by a combination of high performance liquid chromatographic procedures. In order to study Z-riboside metabolism wild-type and mutant cells were cultured in Z-riboside. This ribosyl precursor to a purine de novo intermediate does not undergo any detectable phosphorolysis but rather is phosphorylated by adenosine kinase in an unregulated manner. This results in the intracellular accumulation of 5-amino-4-imidazolecarboxamide ribotide (ZMP), the levels of which control flow from Z-riboside to the following metabolites: 1) IMP and other purine nucleotides, 2) 5-amino-4-imidazole-N-succinocarboxamide ribotide (sZMP), and 3) 5-amino-4-imidazolecarboxamide riboside 5'-triphosphate (ZTP). At low ZMP concentrations, the predominant metabolic fate is IMP. Initially, IMP enters the adenylate and guanylate pools, but subsequently is hydrolyzed to inosine and this phosphorolyzed to hypoxanthine. At intermediate ZMP concentrations there is net retrograde flux through the bifunctional enzyme adenylosuccinate AMP lyase resulting in sZMP synthesis and antegrade flux leads to the accumulation of adenylosuccinate. At high ZMP concentrations, ZTP accumulates. In addition to these effects on purine metabolism, pyrimidine nucleotide pools are depleted when ZMP accumulates. These results are discussed in relation to the regulation of purine nucleotide synthesis and the use of Z-riboside as a pharmacological intervention in pathophysiological situations.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
260
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6107-14
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1985
pubmed:articleTitle
5-Amino-4-imidazolecarboxamide riboside (Z-riboside) metabolism in eukaryotic cells.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't