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Photosensitivity in Smith-Lemli-Opitz syndrome: A flux balance analysis of altered metabolism

Ultraviolet A photosensitivity is a debilitating symptom associated with the metabolic disorder Smith-Lemli-Opitz syndrome (SLOS). SLOS is a manifestation of the deficiency of 7-dehydrocholesterol reductase, an enzyme involved in the cholesterol biosynthesis. As a result several abnormal intermediar...

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Detalles Bibliográficos
Autor principal: Eapen, Bell Raj
Formato: Texto
Lenguaje:English
Publicado: Biomedical Informatics Publishing Group 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174425/
https://www.ncbi.nlm.nih.gov/pubmed/18188427
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author Eapen, Bell Raj
author_facet Eapen, Bell Raj
author_sort Eapen, Bell Raj
collection PubMed
description Ultraviolet A photosensitivity is a debilitating symptom associated with the metabolic disorder Smith-Lemli-Opitz syndrome (SLOS). SLOS is a manifestation of the deficiency of 7-dehydrocholesterol reductase, an enzyme involved in the cholesterol biosynthesis. As a result several abnormal intermediary compounds are formed among which Cholesta 5, 7, 9(11)-trien-3beta-ol is the most likely cause of photosensitivity. The effect of various drugs acting on cholesterol biosynthetic pathway on SLOS is not clear as clinical trials are not available for this rare disorder. A Flux Balance Analysis (FBA) has been carried out using the software CellNetAnalyzer or FluxAnalyzer to gain insight into the probable effects of various drugs acting on cholesterol biosynthetic pathway on photosensitivity in SLOS. The model consisted of 44 metabolites and 40 reactions. The formation flux of Cholesta 5, 7, 9(11)-trien-3beta-ol increased in SLOS and remained unchanged on simulation of the effect of miconazole and SR31747. However zaragozic acid can potentially reduce the flux through the entire pathway. FBA predicts zaragozic acid along with cholesterol supplementation as an effective treatment for photosensitivity in SLOS.
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spelling pubmed-21744252008-01-10 Photosensitivity in Smith-Lemli-Opitz syndrome: A flux balance analysis of altered metabolism Eapen, Bell Raj Bioinformation Prediction Model Ultraviolet A photosensitivity is a debilitating symptom associated with the metabolic disorder Smith-Lemli-Opitz syndrome (SLOS). SLOS is a manifestation of the deficiency of 7-dehydrocholesterol reductase, an enzyme involved in the cholesterol biosynthesis. As a result several abnormal intermediary compounds are formed among which Cholesta 5, 7, 9(11)-trien-3beta-ol is the most likely cause of photosensitivity. The effect of various drugs acting on cholesterol biosynthetic pathway on SLOS is not clear as clinical trials are not available for this rare disorder. A Flux Balance Analysis (FBA) has been carried out using the software CellNetAnalyzer or FluxAnalyzer to gain insight into the probable effects of various drugs acting on cholesterol biosynthetic pathway on photosensitivity in SLOS. The model consisted of 44 metabolites and 40 reactions. The formation flux of Cholesta 5, 7, 9(11)-trien-3beta-ol increased in SLOS and remained unchanged on simulation of the effect of miconazole and SR31747. However zaragozic acid can potentially reduce the flux through the entire pathway. FBA predicts zaragozic acid along with cholesterol supplementation as an effective treatment for photosensitivity in SLOS. Biomedical Informatics Publishing Group 2007-10-26 /pmc/articles/PMC2174425/ /pubmed/18188427 Text en © 2007 Biomedical Informatics Publishing Group This is an open-access article, which permits unrestricted use, distribution, and reproduction in any medium, for non-commercial purposes, provided the original author and source are credited.
spellingShingle Prediction Model
Eapen, Bell Raj
Photosensitivity in Smith-Lemli-Opitz syndrome: A flux balance analysis of altered metabolism
title Photosensitivity in Smith-Lemli-Opitz syndrome: A flux balance analysis of altered metabolism
title_full Photosensitivity in Smith-Lemli-Opitz syndrome: A flux balance analysis of altered metabolism
title_fullStr Photosensitivity in Smith-Lemli-Opitz syndrome: A flux balance analysis of altered metabolism
title_full_unstemmed Photosensitivity in Smith-Lemli-Opitz syndrome: A flux balance analysis of altered metabolism
title_short Photosensitivity in Smith-Lemli-Opitz syndrome: A flux balance analysis of altered metabolism
title_sort photosensitivity in smith-lemli-opitz syndrome: a flux balance analysis of altered metabolism
topic Prediction Model
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174425/
https://www.ncbi.nlm.nih.gov/pubmed/18188427
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