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Ketohexokinase

ketohexokinase, KHK
This gene encodes ketohexokinase that catalyzes conversion of fructose to fructose-1-phosphate. The product of this gene is the first enzyme with a specialized pathway that catabolizes dietary fructose. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008] (from NCBI)
Top mentioned proteins: V1a, CAN, ACID, fibrillin-1, AGE
Papers on ketohexokinase
Pharmacophore modeling, virtual screening, molecular docking studies and density functional theory approaches to identify novel ketohexokinase (KHK) inhibitors.
New
Meganathan et al., India. In Biosystems, Dec 2015
Fructose catabolism starts with phosphorylation of d-fructose to fructose 1-phosphate, which is performed by ketohexokinase (KHK).
Effect of dietary fructose on portal and systemic serum fructose levels in rats and in KHK-/- and GLUT5-/- mice.
New
Ferraris et al., Newark, United States. In Am J Physiol Gastrointest Liver Physiol, Dec 2015
We hypothesized that diet-induced changes in blood fructose concentrations are regulated by ketohexokinase (KHK) and the fructose transporter GLUT5.
Transport, metabolism, and endosomal trafficking-dependent regulation of intestinal fructose absorption.
New
Ferraris et al., Newark, United States. In Faseb J, Sep 2015
We hypothesized that glucose transporter (GLUT) protein, member 5 (GLUT5) is the primary fructose transporter and that fructose absorption via GLUT5, metabolism via ketohexokinase (KHK), as well as GLUT5 trafficking to the apical membrane via the Ras-related protein-in-brain 11 (Rab11)a-dependent endosomes are each required for regulation.
Fructose-induced increases in expression of intestinal fructolytic and gluconeogenic genes are regulated by GLUT5 and KHK.
New
Ferraris et al., Newark, United States. In Am J Physiol Regul Integr Comp Physiol, Sep 2015
We used genetic mouse models to test the hypothesis that fructose absorption via glucose transporter protein, member 5 (GLUT5), metabolism via ketohexokinase (KHK), as well as GLUT5 trafficking to the apical membrane via the Ras-related protein in brain 11a (Rab11a)-dependent endosomes are required for the regulation of intestinal fructolytic and gluconeogenic enzymes.
The phenotype of a knockout mouse identifies flavin-containing monooxygenase 5 (FMO5) as a regulator of metabolic ageing.
New
Shephard et al., London, United Kingdom. In Biochem Pharmacol, Sep 2015
Five proteins were down regulated in the liver of Fmo5(-/-) mice: aldolase B, ketohexokinase and cytosolic glycerol 3-phosphate dehydrogenase (GPD1) are involved in glucose or fructose metabolism and GPD1 also in production of glycerol 3-phosphate, a precursor of triglyceride biosynthesis; HMG-CoA synthase 1 is involved in cholesterol biosynthesis; and malic enzyme 1 catalyzes the oxidative decarboxylation of malate to pyruvate, in the process producing NADPH for use in lipid and cholesterol biosynthesis.
Engineering of a Synthetic Metabolic Pathway for the Assimilation of (d)-Xylose into Value-Added Chemicals.
New
Walther et al., Toulouse, France. In Acs Synth Biol, Aug 2015
Simultaneous expression of xylulose-1 kinase and X1P aldolase activities, provided by human ketohexokinase-C and human aldolase-B, respectively, restored growth of a (d)-xylulose-5-kinase mutant on xylose.
HIF-driven SF3B1 induces KHK-C to enforce fructolysis and heart disease.
New
Impact
Krek et al., Zürich, Switzerland. In Nature, Jul 2015
The central fructose-metabolising enzyme is ketohexokinase (KHK), which exists in two isoforms: KHK-A and KHK-C, generated through mutually exclusive alternative splicing of KHK pre-mRNAs.
Uptake and metabolism of fructose by rat neocortical cells in vivo and by isolated nerve terminals in vitro.
New
Rise et al., Oslo, Norway. In J Neurochem, May 2015
By contrast, the fructose-specific ketohexokinase was weakly expressed.
Sex differences in renal and metabolic responses to a high-fructose diet in mice.
New
Ecelbarger et al., Colombia. In Am J Physiol Renal Physiol, Apr 2015
In male mice, fructose increased the expression (∼50%) of renal cortical proteins involved in metabolism, including glucose transporter 5 (facilitative fructose transporter), ketohexokinase, and the insulin receptor (β-subunit).
Adiponectin resistance and proinflammatory changes in the visceral adipose tissue induced by fructose consumption via ketohexokinase-dependent pathway.
New
Sautin et al., Denver, United States. In Diabetes, Feb 2015
In mammalian cells, fructose is metabolized predominantly via phosphorylation to fructose-1 phosphate by ketohexokinase (KHK) or by alternative pathways.
Demands for carbohydrates as major energy substrates depend on the preimplantation developmental stage in pig embryos: differential use of fructose by parthenogenetic diploids before and after the 4-cell stage in the pig.
Miyake et al., Kōbe, Japan. In J Reprod Dev, 2014
Since ketohexokinase that metabolizes fructose was not expressed in 2-cell and 4-cell diploids, a medium that included only fructose as a major energy substrate did not support early cleavage of pig diploids beyond the 4-cell stage, and almost no diploids developed to the morula stage just as in a medium without carbohydrates.
Endogenous fructose production and fructokinase activation mediate renal injury in diabetic nephropathy.
Johnson et al., Maracaibo, Venezuela. In J Am Soc Nephrol, 2014
However, in the proximal tubule, sorbitol can be converted to fructose, which is then metabolized largely by fructokinase, also known as ketohexokinase, leading to ATP depletion, proinflammatory cytokine expression, and oxidative stress.
Opposing effects of fructokinase C and A isoforms on fructose-induced metabolic syndrome in mice.
GeneRIF
Johnson et al., Aurora, United States. In Proc Natl Acad Sci U S A, 2012
Fructose-induced metabolic syndrome is prevented in mice lacking both fructokinase B and A but is exacerbated in mice lacking fructokinase A.
Liver AMP/ATP ratio and fructokinase expression are related to gender differences in AMPK activity and glucose intolerance in rats ingesting liquid fructose.
GeneRIF
Laguna et al., Barcelona, Spain. In J Nutr Biochem, 2011
Liver expression of the enzyme fructokinase, controlling fructose metabolism, was markedly induced by fructose ingestion in female, but not in male rats.
Inhibitors of Ketohexokinase: Discovery of Pyrimidinopyrimidines with Specific Substitution that Complements the ATP-Binding Site.
Petrounia et al., United States. In Acs Med Chem Lett, 2011
Attenuation of fructose metabolism by the inhibition of ketohexokinase (KHK; fructokinase) should reduce body weight, free fatty acids, and triglycerides, thereby offering a novel approach to treat diabetes and obesity in response to modern diets.
Reduction of liver fructokinase expression and improved hepatic inflammation and metabolism in liquid fructose-fed rats after atorvastatin treatment.
GeneRIF
Laguna et al., Barcelona, Spain. In Toxicol Appl Pharmacol, 2011
Atorvastatin decreased the expression of fructokinase in livers of fructose-supplemented rats, reducing the metabolic burden on the liver that is imposed by continuous fructose ingestion.
Both isoforms of ketohexokinase are dispensable for normal growth and development.
GeneRIF
Bonthron et al., Leeds, United Kingdom. In Physiol Genomics, 2010
These studies are the first demonstration that neither Khk isoform is required for normal growth and development.
Structures of alternatively spliced isoforms of human ketohexokinase.
GeneRIF
Phillips et al., Leeds, United Kingdom. In Acta Crystallogr D Biol Crystallogr, 2009
The structure of the KHK-A ternary complex revealed an active site with fructose & the ATP analogue in positions ready for phosphorylation. The effects of the pathogenic mutations Gly40Arg & Ala43Thr have been modelled in the context of the KHK structure.
Fructose metabolism in the cerebellum.
Review
Tolan et al., Boston, United States. In Cerebellum, 2006
A recent neuro-metabolism study of the cerebellum demonstrated fructose metabolism and co-expression of the genes specific for the fructose 1-phosphate pathway, GLUT5 (glut5) and ketohexokinase (khk), in Purkinje cells suggesting this as an active pathway in specific neurons?
The EMILIN protein family.
Review
Spessotto et al., In Matrix Biol, 2000
The gene for EMILIN-1 was mapped on chromosome 2p23 overlapping with the promoter region of the ketohexokinase gene.
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