| pubmed-article:18429047 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:18429047 | lifeskim:mentions | umls-concept:C0030705 | lld:lifeskim |
| pubmed-article:18429047 | lifeskim:mentions | umls-concept:C0026755 | lld:lifeskim |
| pubmed-article:18429047 | lifeskim:mentions | umls-concept:C0205082 | lld:lifeskim |
| pubmed-article:18429047 | lifeskim:mentions | umls-concept:C1415593 | lld:lifeskim |
| pubmed-article:18429047 | lifeskim:mentions | umls-concept:C0392756 | lld:lifeskim |
| pubmed-article:18429047 | lifeskim:mentions | umls-concept:C0018517 | lld:lifeskim |
| pubmed-article:18429047 | pubmed:issue | 6 | lld:pubmed |
| pubmed-article:18429047 | pubmed:dateCreated | 2008-5-28 | lld:pubmed |
| pubmed-article:18429047 | pubmed:abstractText | Multiple carboxylase deficiency is a clinical condition caused by defects in the enzymes involved in biotin metabolism, holocarboxylase synthetase (HLCS) or biotinidase. HLCS deficiency is a potentially fatal condition if left untreated, although the majority of patients respond to oral supplementation of 10-20 mg/day of biotin. Patients who display incomplete responsiveness to this therapy have a poor long-term prognosis. Here we investigated cell lines from two such HLCS-deficient patients homozygous for the c.647T>G p.L216R allele. Growth of the patients' fibroblasts was compromised compared with normal fibroblasts. Also the patient cells were not sensitive to biotin-depletion from the media, and growth rates could not be restored by re-administration of biotin. The molecular basis for the HLCS deficiency was further investigated by characterisation of the p.L216R protein. The HLCS mRNA was detected in MCD and normal cell lines. However, protein and enzyme activity could not be detected in the patients' cells. In vitro kinetic analysis revealed that enzyme activity was severely compromised for recombinantly expressed p.L216R and could not be increased by additional biotin. Furthermore, the turn-over rate for the mutant protein was double that of wildtype HLCS. These results help provide a molecular explanation for the incomplete biotin-responsiveness of this p.L216R form of HLCS. | lld:pubmed |
| pubmed-article:18429047 | pubmed:language | eng | lld:pubmed |
| pubmed-article:18429047 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18429047 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:18429047 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18429047 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18429047 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18429047 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:18429047 | pubmed:month | Jun | lld:pubmed |
| pubmed-article:18429047 | pubmed:issn | 1098-1004 | lld:pubmed |
| pubmed-article:18429047 | pubmed:author | pubmed-author:WallaceJohn... | lld:pubmed |
| pubmed-article:18429047 | pubmed:author | pubmed-author:WilsonCallum... | lld:pubmed |
| pubmed-article:18429047 | pubmed:author | pubmed-author:JitrapakdeeSa... | lld:pubmed |
| pubmed-article:18429047 | pubmed:author | pubmed-author:BaileyLisa... | lld:pubmed |
| pubmed-article:18429047 | pubmed:author | pubmed-author:PolyakSteven... | lld:pubmed |
| pubmed-article:18429047 | pubmed:author | pubmed-author:IvanovRuby... | lld:pubmed |
| pubmed-article:18429047 | pubmed:copyrightInfo | (c) 2008 Wiley-Liss, Inc. | lld:pubmed |
| pubmed-article:18429047 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:18429047 | pubmed:volume | 29 | lld:pubmed |
| pubmed-article:18429047 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:18429047 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:18429047 | pubmed:pagination | E47-57 | lld:pubmed |
| pubmed-article:18429047 | pubmed:meshHeading | pubmed-meshheading:18429047... | lld:pubmed |
| pubmed-article:18429047 | pubmed:meshHeading | pubmed-meshheading:18429047... | lld:pubmed |
| pubmed-article:18429047 | pubmed:meshHeading | pubmed-meshheading:18429047... | lld:pubmed |
| pubmed-article:18429047 | pubmed:meshHeading | pubmed-meshheading:18429047... | lld:pubmed |
| pubmed-article:18429047 | pubmed:meshHeading | pubmed-meshheading:18429047... | lld:pubmed |
| pubmed-article:18429047 | pubmed:meshHeading | pubmed-meshheading:18429047... | lld:pubmed |
| pubmed-article:18429047 | pubmed:meshHeading | pubmed-meshheading:18429047... | lld:pubmed |
| pubmed-article:18429047 | pubmed:meshHeading | pubmed-meshheading:18429047... | lld:pubmed |
| pubmed-article:18429047 | pubmed:meshHeading | pubmed-meshheading:18429047... | lld:pubmed |
| pubmed-article:18429047 | pubmed:meshHeading | pubmed-meshheading:18429047... | lld:pubmed |
| pubmed-article:18429047 | pubmed:meshHeading | pubmed-meshheading:18429047... | lld:pubmed |
| pubmed-article:18429047 | pubmed:meshHeading | pubmed-meshheading:18429047... | lld:pubmed |
| pubmed-article:18429047 | pubmed:year | 2008 | lld:pubmed |
| pubmed-article:18429047 | pubmed:articleTitle | Reduced half-life of holocarboxylase synthetase from patients with severe multiple carboxylase deficiency. | lld:pubmed |
| pubmed-article:18429047 | pubmed:affiliation | School of Molecular and Biomedical Science, The University of Adelaide, Adelaide, South Australia 5005, Australia. | lld:pubmed |
| pubmed-article:18429047 | pubmed:publicationType | Journal Article | lld:pubmed |
| entrez-gene:3141 | entrezgene:pubmed | pubmed-article:18429047 | lld:entrezgene |
| http://linkedlifedata.com/r... | entrezgene:pubmed | pubmed-article:18429047 | lld:entrezgene |
