Linked Life Data

3752080

Source:http://linkedlifedata.com/resource/pubmed/id/3752080

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1986-10-3
pubmed:abstractText
Argininosuccinate lyase (AS lyase) deficiency is an inborn error of the urea cycle with extensive clinical and genetic heterogeneity. We investigated the biochemical basis of the enzyme defect and the genetic heterogeneity in this disorder using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting of fibroblast extracts. The AS lyase monomer in control fibroblasts was present in two bands of approximately 51 and approximately 49 Kd. Each of 28 mutant strains had some cross-reactive material (CRM) of the lower (approximately 49 Kd) MW, in quantities ranging from trace to substantial levels. The approximately 51 Kd band was found in only six mutants with near-normal amounts of AS lyase CRM or high residual enzyme activity. The residual AS lyase enzyme activity in a mutant did not necessarily reflect the amount of the 49-51 Kd monomer in that strain. In contrast, there was a strong general correlation between the quantity of 49-51 Kd CRM in a mutant and the frequency of complementation by that mutant. In addition to the CRM of normal molecular weight (MW) (49-51 Kd), the majority of mutants (but not controls) had significant CRM present in one to five bands of MW less than 49 Kd. The immunoprecipitation of at least one of these low MW bands was inhibited by purified human AS lyase. Mutants indistinguishable by clinical, enzymatic, or complementation analysis have been shown to be heterogeneous in their content of AS lyase CRM, greatly extending the number of distinct mutant alleles identified at this locus. These data demonstrate that multiple unique mutations in the structural gene coding for the monomer cause AS lyase deficiency and that the AS lyase monomers made by these mutants may be unstable. Integration of these findings with enzymatic and complementation data has indicated the functional domain of the AS lyase monomer likely to be altered in certain mutants.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/3752080-14149958, http://linkedlifedata.com/resource/pubmed/commentcorrection/3752080-14907713, http://linkedlifedata.com/resource/pubmed/commentcorrection/3752080-388439, http://linkedlifedata.com/resource/pubmed/commentcorrection/3752080-4531013, http://linkedlifedata.com/resource/pubmed/commentcorrection/3752080-5279808, http://linkedlifedata.com/resource/pubmed/commentcorrection/3752080-5432063, http://linkedlifedata.com/resource/pubmed/commentcorrection/3752080-6287917, http://linkedlifedata.com/resource/pubmed/commentcorrection/3752080-6386606, http://linkedlifedata.com/resource/pubmed/commentcorrection/3752080-6424438, http://linkedlifedata.com/resource/pubmed/commentcorrection/3752080-6589607, http://linkedlifedata.com/resource/pubmed/commentcorrection/3752080-6784763, http://linkedlifedata.com/resource/pubmed/commentcorrection/3752080-6823295, http://linkedlifedata.com/resource/pubmed/commentcorrection/3752080-7263708
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0002-9297
pubmed:author
pubmed:issnType
Print
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
38-51
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1986
pubmed:articleTitle
Argininosuccinate lyase deficiency: evidence for heterogeneous structural gene mutations by immunoblotting.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't