A compendium of inborn errors of metabolism mapped onto the human metabolic network.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
CitationMol. Biosyst. 2012, 8(10):2545-58
AbstractInborn errors of metabolism (IEMs) are hereditary metabolic defects, which are encountered in almost all major metabolic pathways occurring in man. Many IEMs are screened for in neonates through metabolomic analysis of dried blood spot samples. To enable the mapping of these metabolomic data onto the published human metabolic reconstruction, we added missing reactions and pathways involved in acylcarnitine (AC) and fatty acid oxidation (FAO) metabolism. Using literary data, we reconstructed an AC/FAO module consisting of 352 reactions and 139 metabolites. When this module was combined with the human metabolic reconstruction, the synthesis of 39 acylcarnitines and 22 amino acids, which are routinely measured, was captured and 235 distinct IEMs could be mapped. We collected phenotypic and clinical features for each IEM enabling comprehensive classification. We found that carbohydrate, amino acid, and lipid metabolism were most affected by the IEMs, while the brain was the most commonly affected organ. Furthermore, we analyzed the IEMs in the context of metabolic network topology to gain insight into common features between metabolically connected IEMs. While many known examples were identified, we discovered some surprising IEM pairs that shared reactions as well as clinical features but not necessarily causal genes. Moreover, we could also re-confirm that acetyl-CoA acts as a central metabolite. This network based analysis leads to further insight of hot spots in human metabolism with respect to IEMs. The presented comprehensive knowledge base of IEMs will provide a valuable tool in studying metabolic changes involved in inherited metabolic diseases.
DescriptionEfst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn
- The screening of inborn errors of metabolism in sick Chinese infants by tandem mass spectrometry and gas chromatography/mass spectrometry.
- Authors: Sun W, Wang Y, Yang Y, Wang J, Cao Y, Luo F, Lu W, Peng Y, Yao H, Qiu P
- Issue date: 2011 Jun 11
- [Study of plasma acylcarnitines using tandem mass spectrometry. Application to the diagnosis of metabolism hereditary diseases].
- Authors: Delolme F, Vianey-Saban C, Guffon N, Favre-Bonvin J, Guibaud P, Becchi M, Mathieu M, Divry P
- Issue date: 1997 Sep
- Electrospray tandem mass spectrometry for analysis of acylcarnitines in dried postmortem blood specimens collected at autopsy from infants with unexplained cause of death.
- Authors: Chace DH, DiPerna JC, Mitchell BL, Sgroi B, Hofman LF, Naylor EW
- Issue date: 2001
- A novel functional assay for simultaneous determination of total fatty acid beta-oxidation flux and acylcarnitine profiling in human skin fibroblasts using (2)H(31)-palmitate by isotope ratio mass spectrometry and electrospray tandem mass spectrometry.
- Authors: Law LK, Tang NL, Hui J, Ho CS, Ruiter J, Fok TF, Wanders RJ, Lam CW
- Issue date: 2007 Jul
- Quantitative fibroblast acylcarnitine profiles in mitochondrial fatty acid beta-oxidation defects: phenotype/metabolite correlations.
- Authors: Giak Sim K, Carpenter K, Hammond J, Christodoulou J, Wilcken B
- Issue date: 2002 Aug