Biochemical characterization of human gluconokinase and the proposed metabolic impact of gluconic acid as determined by constraint based metabolic network analysis.

The metabolism of gluconate is well characterized in prokaryotes where it is known to be degraded following phosphorylation by gluconokinase. Less is known of gluconate metabolism in humans. Human gluconokinase activity was recently identified proposing questions about the metabolic role of gluconat...

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Autores principales:	Neha Rohatgi, Tine Kragh Nielsen, Sara Petersen Bjørn, Ivar Axelsson, Giuseppe Paglia, Bjørn Gunnar Voldborg, Bernhard O Palsson, Óttar Rolfsson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6d498c11c8b34c40a1f5afa496f645cb
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spelling	oai:doaj.org-article:6d498c11c8b34c40a1f5afa496f645cb2021-11-18T08:17:13ZBiochemical characterization of human gluconokinase and the proposed metabolic impact of gluconic acid as determined by constraint based metabolic network analysis.1932-620310.1371/journal.pone.0098760https://doaj.org/article/6d498c11c8b34c40a1f5afa496f645cb2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24896608/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The metabolism of gluconate is well characterized in prokaryotes where it is known to be degraded following phosphorylation by gluconokinase. Less is known of gluconate metabolism in humans. Human gluconokinase activity was recently identified proposing questions about the metabolic role of gluconate in humans. Here we report the recombinant expression, purification and biochemical characterization of isoform I of human gluconokinase alongside substrate specificity and kinetic assays of the enzyme catalyzed reaction. The enzyme, shown to be a dimer, had ATP dependent phosphorylation activity and strict specificity towards gluconate out of 122 substrates tested. In order to evaluate the metabolic impact of gluconate in humans we modeled gluconate metabolism using steady state metabolic network analysis. The results indicate that significant metabolic flux changes in anabolic pathways linked to the hexose monophosphate shunt (HMS) are induced through a small increase in gluconate concentration. We argue that the enzyme takes part in a context specific carbon flux route into the HMS that, in humans, remains incompletely explored. Apart from the biochemical description of human gluconokinase, the results highlight that little is known of the mechanism of gluconate metabolism in humans despite its widespread use in medicine and consumer products.Neha RohatgiTine Kragh NielsenSara Petersen BjørnIvar AxelssonGiuseppe PagliaBjørn Gunnar VoldborgBernhard O PalssonÓttar RolfssonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 6, p e98760 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Neha Rohatgi Tine Kragh Nielsen Sara Petersen Bjørn Ivar Axelsson Giuseppe Paglia Bjørn Gunnar Voldborg Bernhard O Palsson Óttar Rolfsson Biochemical characterization of human gluconokinase and the proposed metabolic impact of gluconic acid as determined by constraint based metabolic network analysis.
description	The metabolism of gluconate is well characterized in prokaryotes where it is known to be degraded following phosphorylation by gluconokinase. Less is known of gluconate metabolism in humans. Human gluconokinase activity was recently identified proposing questions about the metabolic role of gluconate in humans. Here we report the recombinant expression, purification and biochemical characterization of isoform I of human gluconokinase alongside substrate specificity and kinetic assays of the enzyme catalyzed reaction. The enzyme, shown to be a dimer, had ATP dependent phosphorylation activity and strict specificity towards gluconate out of 122 substrates tested. In order to evaluate the metabolic impact of gluconate in humans we modeled gluconate metabolism using steady state metabolic network analysis. The results indicate that significant metabolic flux changes in anabolic pathways linked to the hexose monophosphate shunt (HMS) are induced through a small increase in gluconate concentration. We argue that the enzyme takes part in a context specific carbon flux route into the HMS that, in humans, remains incompletely explored. Apart from the biochemical description of human gluconokinase, the results highlight that little is known of the mechanism of gluconate metabolism in humans despite its widespread use in medicine and consumer products.
format	article
author	Neha Rohatgi Tine Kragh Nielsen Sara Petersen Bjørn Ivar Axelsson Giuseppe Paglia Bjørn Gunnar Voldborg Bernhard O Palsson Óttar Rolfsson
author_facet	Neha Rohatgi Tine Kragh Nielsen Sara Petersen Bjørn Ivar Axelsson Giuseppe Paglia Bjørn Gunnar Voldborg Bernhard O Palsson Óttar Rolfsson
author_sort	Neha Rohatgi
title	Biochemical characterization of human gluconokinase and the proposed metabolic impact of gluconic acid as determined by constraint based metabolic network analysis.
title_short	Biochemical characterization of human gluconokinase and the proposed metabolic impact of gluconic acid as determined by constraint based metabolic network analysis.
title_full	Biochemical characterization of human gluconokinase and the proposed metabolic impact of gluconic acid as determined by constraint based metabolic network analysis.
title_fullStr	Biochemical characterization of human gluconokinase and the proposed metabolic impact of gluconic acid as determined by constraint based metabolic network analysis.
title_full_unstemmed	Biochemical characterization of human gluconokinase and the proposed metabolic impact of gluconic acid as determined by constraint based metabolic network analysis.
title_sort	biochemical characterization of human gluconokinase and the proposed metabolic impact of gluconic acid as determined by constraint based metabolic network analysis.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/6d498c11c8b34c40a1f5afa496f645cb
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Biochemical characterization of human gluconokinase and the proposed metabolic impact of gluconic acid as determined by constraint based metabolic network analysis.

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