Linked Life Data

1885764

Source:http://linkedlifedata.com/resource/pubmed/id/1885764

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1991-10-4
pubmed:abstractText
Maple Syrup Urine Disease (MSUD) in Mennonites is associated with homozygosity for a T to A transversion in the E1 alpha gene of the branched-chain alpha-keto acid dehydrogenase complex. This causes a tyrosine to asparagine substitution at position 393 (Y393N). To assess the functional significance of this missense mutation, we have carried out transfection studies using E1 alpha-deficient MSUD lymphoblasts (Lo) as a host. The level of E1 beta subunit is also greatly reduced in Lo cells. Efficient episomal expression in lymphoblasts was achieved using the EBO vector. The inserts employed were chimeric bovine-human cDNAs which encode mitochondrial import competent E1 alpha subunit precursors. Transfection with normal E1 alpha cDNA into Lo cells restored decarboxylation activity of intact cells. Western blotting showed that both E1 alpha and E1 beta subunits were markedly increased. Introduction of Y393N mutant E1 alpha cDNA failed to produce any measurable decarboxylation activity. Mutant E1 alpha subunit was expressed at a normal level, however, the E1 beta subunit was undetectable. These results provide the first evidence that Y393N mutation is the cause of MSUD. Moreover, this mutation impedes the assembly of E1 alpha with E1 beta into a stable alpha 2 beta 2 structure, resulting in the degradation of the free E1 beta subunit.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/1885764-13214961, http://linkedlifedata.com/resource/pubmed/commentcorrection/1885764-1867199, http://linkedlifedata.com/resource/pubmed/commentcorrection/1885764-2004553, http://linkedlifedata.com/resource/pubmed/commentcorrection/1885764-2060625, http://linkedlifedata.com/resource/pubmed/commentcorrection/1885764-2303405, http://linkedlifedata.com/resource/pubmed/commentcorrection/1885764-2335211, http://linkedlifedata.com/resource/pubmed/commentcorrection/1885764-2649080, http://linkedlifedata.com/resource/pubmed/commentcorrection/1885764-2703538, http://linkedlifedata.com/resource/pubmed/commentcorrection/1885764-2822716, http://linkedlifedata.com/resource/pubmed/commentcorrection/1885764-2841588, http://linkedlifedata.com/resource/pubmed/commentcorrection/1885764-3071697, http://linkedlifedata.com/resource/pubmed/commentcorrection/1885764-3140238, http://linkedlifedata.com/resource/pubmed/commentcorrection/1885764-3379058, http://linkedlifedata.com/resource/pubmed/commentcorrection/1885764-4346033, http://linkedlifedata.com/resource/pubmed/commentcorrection/1885764-6312838, http://linkedlifedata.com/resource/pubmed/commentcorrection/1885764-7108955
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9738
pubmed:author
pubmed:issnType
Print
pubmed:volume
88
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1034-7
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
Maple syrup urine disease in Mennonites. Evidence that the Y393N mutation in E1 alpha impedes assembly of the E1 component of branched-chain alpha-keto acid dehydrogenase complex.
pubmed:affiliation
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't