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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
- Source :
- PloS one, vol 9, iss 6, PLoS ONE, PLoS ONE, Vol 9, Iss 6, p e98760 (2014)
- Publication Year :
- 2014
- Publisher :
- eScholarship, University of California, 2014.
-
Abstract
- To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access. 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. info:eu-repo/grantAgreement/EC/FP7/232816
- Subjects :
- Models, Molecular
Erythrocytes
Protein Conformation
Biochemistry
Substrate Specificity
chemistry.chemical_compound
Models
Biochemical Simulations
Phosphorylation
chemistry.chemical_classification
Multidisciplinary
Systems Biology
Enzymes
3. Good health
Phosphotransferases (Alcohol Group Acceptor)
Medicine
Carbohydrate Metabolism
Metabolic Pathways
Network Analysis
Metabolic Networks and Pathways
Research Article
Biotechnology
Computer and Information Sciences
General Science & Technology
Science
Pentose phosphate pathway
Biology
Gluconates
Metabolic Networks
Clinical Research
Escherichia coli
Humans
Theoretical Biology
Enzyme Kinetics
Phosphotransferases
Biology and Life Sciences
Proteins
Computational Biology
Molecular
Metabolism
Gluconokinase
Kinetics
Enzyme
chemistry
Small Molecules
Enzymology
Gluconic acid
Gluconokinase activity
Flux (metabolism)
Drug metabolism
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- PloS one, vol 9, iss 6, PLoS ONE, PLoS ONE, Vol 9, Iss 6, p e98760 (2014)
- Accession number :
- edsair.doi.dedup.....8380a968362397108e5bbe04314cb339