Linked Life Data

15050969

Source:http://linkedlifedata.com/resource/pubmed/id/15050969

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2004-3-30
pubmed:abstractText
Carbamyl phosphate synthetase I (CPSI) determines the rate-limiting entry of free ammonia into the urea cycle. Disruption of CPSI affects the liver's ability to remove waste nitrogen and produce arginine, citrulline, and urea. Arginine is the necessary precursor for the critical biomolecule, nitric oxide (NO). We have studied the classic model of CPSI deficiency, which results in severe hyperammonemia, and identified a large number of molecular defects. A number of CPSI polymorphisms have been found that appear to result in functional consequences. We have examined the association of these polymorphisms with various environmental stress conditions and found that certain CPSI alleles are associated with clinical outcome. We refer to these associations as environmentally determined genetic expression (EDGE) affects. In addition to studies of classic CPSI deficiency, we have developed data for the EDGE concept in post-cardiac surgery-related pulmonary hypertension, hepatic veno-occlusive disease after bone marrow transplantation, and persistent pulmonary hypertension of the newborn. We have linked these outcomes and genotypes to the availability of the urea cycle intermediates, citrulline and arginine, and their role in NO synthesis. We hypothesize that these polymorphisms affect the functional efficiency of CPSI and thus the entire urea cycle and as such, the availability of the NO substrates. By piecing together the various functional aspects of the urea cycle changes we have seen, we can better understand the clinical vulnerabilities of patients in environmentally stressful situations. This knowledge should allow us to design intervention strategies to either predict or modify the associated adverse outcomes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1096-7192
pubmed:author
pubmed:issnType
Print
pubmed:volume
81 Suppl 1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
S12-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Environmentally determined genetic expression: clinical correlates with molecular variants of carbamyl phosphate synthetase I.
pubmed:affiliation
Division of Medical Genetics, Department of Pediatrics and Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN 37232, USA. marshall.summar@vanderbilt.edu
pubmed:publicationType
Journal Article