Linked Life Data

2881300

Source:http://linkedlifedata.com/resource/pubmed/id/2881300

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1987-4-6
pubmed:abstractText
Methylmalonyl-CoA mutase (2-methylmalonyl-CoA CoA-carbonylmutase, EC 5.4.99.2) is a mitochondrial enzyme whose deficiency in man leads to several biochemically and clinically heterogenous++ forms of methylmalonic acidemia. Intact fibroblasts from 21 patients with mutase apoenzyme deficiency have been pulse-labeled with [3H]leucine or [35S]methionine to determine how amounts of newly synthesized mutase recovered from these cells by immunoprecipitation compare with the amounts of steady-state crossreacting material previously determined. Ten lines (3 mut-, 7 mut 0 ), previously shown to have detectable steady-state crossreacting material, had amounts of newly synthesized mutase that varied from similar (7 lines) to considerably greater than (3 lines) the steady-state amounts. Of 11 lines that had no detectable steady-state crossreacting material, 6 had no detectable newly synthesized mutase, and 5 had amounts of mutase ranging from just detectable to almost half that of control. This result suggests that, at least for this latter group, one effect of the mutation in the mutase gene is to reduce the stability of the mutase protein. We examined fibroblasts from 48 patients with mutase apoenzyme deficiency to determine the sizes of the mature mutase subunit and the mutase precursor accumulated in the presence of the mitochondrial transport inhibitor rhodamine 6G. Of the 38 lines that had detectable newly synthesized mutase, only 2, lines 437 and 552, showed a pattern different from that generated by the normal precursor and mature subunits. Line 437 had two immunoprecipitable precursor proteins in the presence of rhodamine, each of which appeared to be transported and processed in the cells to produce two distinct mature proteins. Line 552 also had two anti-mutase reactive proteins in the presence of rhodamine, but each was smaller than the normal mature subunit and neither appeared to be proteolytically processed. The defect in line 552 is almost certainly an amino-terminal deletion that removes the leader peptide necessary for proper uptake and cleavage of the mutase precursor; this represents a clear example of a natural human mutation that interferes with mitochondrial transport of a protein.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/2881300-20894, http://linkedlifedata.com/resource/pubmed/commentcorrection/2881300-2941675, http://linkedlifedata.com/resource/pubmed/commentcorrection/2881300-3731270, http://linkedlifedata.com/resource/pubmed/commentcorrection/2881300-3748657, http://linkedlifedata.com/resource/pubmed/commentcorrection/2881300-3863140, http://linkedlifedata.com/resource/pubmed/commentcorrection/2881300-3891325, http://linkedlifedata.com/resource/pubmed/commentcorrection/2881300-3943133, http://linkedlifedata.com/resource/pubmed/commentcorrection/2881300-3988798, http://linkedlifedata.com/resource/pubmed/commentcorrection/2881300-4275428, http://linkedlifedata.com/resource/pubmed/commentcorrection/2881300-518835, http://linkedlifedata.com/resource/pubmed/commentcorrection/2881300-6101601, http://linkedlifedata.com/resource/pubmed/commentcorrection/2881300-6121323, http://linkedlifedata.com/resource/pubmed/commentcorrection/2881300-6144679, http://linkedlifedata.com/resource/pubmed/commentcorrection/2881300-6711564
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0027-8424
pubmed:author
pubmed:issnType
Print
pubmed:volume
84
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1421-4
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
1987
pubmed:articleTitle
Immunochemical studies of fibroblasts from patients with methylmalonyl-CoA mutase apoenzyme deficiency: detection of a mutation interfering with mitochondrial import.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.