Linked Life Data

14680974

Source:http://linkedlifedata.com/resource/pubmed/id/14680974

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-12-18
pubmed:abstractText
To evaluate the presumed peroxisomal involvement in cholesterol/isoprenoid biosynthesis, we determined the protein levels and activities of five different enzymes of the presqualene segment of the cholesterol/isoprenoid biosynthetic pathway in primary skin fibroblasts of selected patients with a peroxisomal biogenesis disorder (PBD). These five enzymes all have been reported to be partly or exclusively peroxisomal and include HMG-CoA reductase, mevalonate kinase, phosphomevalonate kinase, mevalonate pyrophosphate decarboxylase, and isopentenyl pyrophosphate isomerase. To exclude that genetic differences, resulting in different defects in peroxisomal biogenesis, have differential effects on the activity of the cholesterol biosynthetic enzymes and on de novo cholesterol biosynthesis, we chose fibroblasts of patients with defined defects in one of four different PEX genes leading to Zellweger syndrome (PEX1, PEX5, PEX16 or PEX19). We found that all enzymes measured are at least as active in the peroxisome-deficient cells cultured in cholesterol-depleted medium as in identically cultured control cells. This indicates that if these presumed peroxisomal proteins are mislocalized to the cytosol they do not loose their activity, nor get degraded unlike most other authentic peroxisomal proteins. We also measured de novo cholesterol synthesis from radio-labeled acetate in all cell lines and found similar or even elevated rates for the PBD cells when compared to controls. Our results imply that functional peroxisomes are not a prerequisite for the functioning of enzymes involved in cholesterol/isoprenoid biosynthesis and as such raise doubts about the true involvement of peroxisomes therein.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Carbon-Carbon Double Bond Isomerases, http://linkedlifedata.com/resource/pubmed/chemical/Carboxy-Lyases, http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol, http://linkedlifedata.com/resource/pubmed/chemical/Hydroxymethylglutaryl CoA Reductases, http://linkedlifedata.com/resource/pubmed/chemical/PHEX Phosphate Regulating Neutral..., http://linkedlifedata.com/resource/pubmed/chemical/PHEX protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Phosphotransferases (Alcohol Group..., http://linkedlifedata.com/resource/pubmed/chemical/Phosphotransferases (Phosphate..., http://linkedlifedata.com/resource/pubmed/chemical/Proteins, http://linkedlifedata.com/resource/pubmed/chemical/isopentenyldiphosphate..., http://linkedlifedata.com/resource/pubmed/chemical/mevalonate kinase, http://linkedlifedata.com/resource/pubmed/chemical/phosphomevalonate kinase, http://linkedlifedata.com/resource/pubmed/chemical/pyrophosphomevalonate decarboxylase
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1096-7192
pubmed:author
pubmed:issnType
Print
pubmed:volume
80
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
290-5
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Cholesterol biosynthesis is not defective in peroxisome biogenesis defective fibroblasts.
pubmed:affiliation
Laboratory Genetic Metabolic Diseases, Department of Pediatrics, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't