Document Detail

Metabolite proofreading, a neglected aspect of intermediary metabolism.
MedLine Citation:
PMID:  23296366     Owner:  NLM     Status:  Publisher    
Enzymes of intermediary metabolism are less specific than what is usually assumed: they often act on metabolites that are not their 'true' substrate, making abnormal metabolites that may be deleterious if they accumulate. Some of these abnormal metabolites are reconverted to normal metabolites by repair enzymes, which play therefore a role akin to the proofreading activities of DNA polymerases and aminoacyl-tRNA synthetases. An illustrative example of such repair enzymes is L-2-hydroxyglutarate dehydrogenase, which eliminates a metabolite abnormally made by a Krebs cycle enzyme. Mutations in L-2-hydroxyglutarate dehydrogenase lead to L-2-hydroxyglutaric aciduria, a leukoencephalopathy. Other examples are the epimerase and the ATP-dependent dehydratase that repair hydrated forms of NADH and NADPH; ethylmalonyl-CoA decarboxylase, which eliminates an abnormal metabolite formed by acetyl-CoA carboxylase, an enzyme of fatty acid synthesis; L-pipecolate oxidase, which repairs a metabolite formed by a side activity of an enzyme of L-proline biosynthesis. Metabolite proofreading enzymes are likely quite common, but most of them are still unidentified. A defect in these enzymes may account for new metabolic disorders.
Emile Van Schaftingen; Rim Rzem; Alexandre Marbaix; François Collard; Maria Veiga-da-Cunha; Carole L Linster
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-8
Journal Detail:
Title:  Journal of inherited metabolic disease     Volume:  -     ISSN:  1573-2665     ISO Abbreviation:  J. Inherit. Metab. Dis.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7910918     Medline TA:  J Inherit Metab Dis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Welbio and de Duve Institute, Université catholique de Louvain, Avenue Hippocrate 75, 1200, Brussels, Belgium,
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