References of "Van Schaftingen, E"
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See detailMetabolite proofreading, a neglected aspect of intermediary metabolism
Van Schaftingen, E.; Rzem, R.; Marbaix, A. et al

in Journal of Inherited Metabolic Disease (2013), 36(3), 427-34

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 ... [more ▼]

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. [less ▲]

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See detailMetabolite damage and its repair or pre-emption
Linster, Carole UL; Van Schaftingen, E.; Hanson, A. D.

in Nature Chemical Biology (2013), 9(2), 72-80

It is increasingly evident that metabolites suffer various kinds of damage, that such damage happens in all organisms, and that cells have dedicated systems for damage repair and containment. Firstly ... [more ▼]

It is increasingly evident that metabolites suffer various kinds of damage, that such damage happens in all organisms, and that cells have dedicated systems for damage repair and containment. Firstly, chemical biology is demonstrating that diverse metabolites are damaged by side-reactions of ‘promiscuous’ enzymes or by spontaneous chemical reactions, that the products are useless or toxic, and that the unchecked buildup of these products can be devastating. Secondly, genetic and genomic evidence from pro- and eukaryotes is implicating a network of novel, conserved enzymes that repair damaged metabolites or somehow pre-empt damage. Metabolite (i.e. small molecule) repair is analogous to macromolecule (DNA and protein) repair and appears from comparative genomic evidence to be equally widespread. Comparative genomics also implies that metabolite repair could be the function of many conserved protein families lacking known activities. How – and how well – cells deal with metabolite damage impacts fields ranging from medical genetics to metabolic engineering. [less ▲]

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