| Accelerating unimolecular decarboxylation by preassociated acid catalysis in thiamin-derived intermediates: implicating Brønsted acids as carbanion traps in enzymes. | |
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MedLine Citation:
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PMID: 17147398 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Mandelylthiamin (MT) is formally the conjugate of thiamin and benzoylformate. It is the simplified analogue of the first covalent intermediate in benzoylformate decarboxylase. Although MT is the functional equivalent of the enzymic intermediate, it is 106-fold less reactive in decarboxylation. Furthermore, upon loss of carbon dioxide, it undergoes a fragmentation reaction that is about 102-fold faster than the enzymic reaction. While Brønsted acids in general can suppress the fragmentation to some extent, they do not accelerate the decarboxylation. Surprisingly, the conjugate acid of pyridine accelerates decarboxylation; it also blocks fragmentation with particularly high efficiency. These results are consistent with the conjugate acid of pyridine acting as a "spectator" catalyst, associating with MT prior to decarboxylation. In the absence of catalyst, carbon dioxide formed upon carbon-carbon bond breaking overwhelmingly reverts to the carboxylate. Association of pyridine (and its conjugate acid) with MT permits trapping of the nascent carbanion by protonation, while nonassociated acids must arrive by the relatively slow process of diffusion. C-Alkyl pyridine acids provide similar catalysis while other acids have no effect. This suggests that an enzyme that generates an aldehyde from a 2-ketoacid should have functional Brønsted acids in their active sites that would trap the carbanion, as does benzoylformate decarboxylase. Enzymes that give nonaldehydic products from decarboxylation of thiamin diphosphate conjugates containing an associated electron acceptor or electrophilic substrate would also be able to prevent the reversal of decarboxylation. |
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Authors:
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Ronald Kluger; Glenn Ikeda; Qingyan Hu; Pengpeng Cao; Joel Drewry |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of the American Chemical Society Volume: 128 ISSN: 0002-7863 ISO Abbreviation: J. Am. Chem. Soc. Publication Date: 2006 Dec |
Date Detail:
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Created Date: 2006-12-06 Completed Date: 2007-03-01 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7503056 Medline TA: J Am Chem Soc Country: United States |
Other Details:
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Languages: eng Pagination: 15856-64 Citation Subset: IM |
Affiliation:
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Davenport Chemical Research Laboratories, Department of Chemistry, University of Toronto, Toronto, Ontario, Canada M5S 3H6. rkluger@chem.utoronto.ca |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acids
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chemistry* Binding Sites Carbon Dioxide / chemistry Carboxy-Lyases / chemistry, metabolism* Catalysis Decarboxylation Glyoxylates / chemistry* Hydrogen-Ion Concentration Kinetics Mandelic Acids / chemistry* Models, Chemical Organophosphorus Compounds / chemistry Pyridines / chemistry Thiamine / analogs & derivatives*, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Acids; 0/Glyoxylates; 0/Mandelic Acids; 0/Organophosphorus Compounds; 0/Pyridines; 110-86-1/pyridine; 124-38-9/Carbon Dioxide; 59-43-8/Thiamine; 611-73-4/phenylglyoxylic acid; EC 4.1.1.-/Carboxy-Lyases; EC 4.1.1.7/benzoylformate decarboxylase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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