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Background: Ketohexokinase, also called as Fructokinase or KHK, can catalyze the phosphorylation of the ketose sugar fructose to fructose-1-phosphate. A number of other furanose sugars can also act as KHK substrates. KHK has two isoforms, KHK-A and KHK-C. KHK-C has a 10-fold higher affinity for fructose (Km = 0.8 mM) and is mainly responsible for its metabolism..KHK-C is expressed primarily in liver while KHK-A is expressed at low levels in a wide range of tissues, and its physiological substrate remains unknown. Liver is the primary organ that metabolizes most of the ingested fructose, the small intestine strongly expresses all fructose-metabolizing enzymes and is responsible for the catabolism of 10-30% of ingested fructose. Fructolysis is initiated by KHK which converts fructose and ATP into fructose 1-phosphate and ADP, respectively. Aldolase-B cleaves fructose 1-phosphate into three-carbon intermediates, dihydroxyacetone phosphate and glyceraldehyde, and the latter is then converted by triokinase into glyceraldehyde 3-phosphate, which then joins the glycolysis pathway. Fructose catabolism initiated by KHK therefore bypasses important glycolytic regulatory steps in glycolysisthatgeneratefructose1,6- bisphosphatethroughtheaction oftheenergy-sensitiveenzymephosphofructokinase(PFK),resulting in greater lipogenesis than that resulting from glycolysis-regulated lipid production. In addition, fructose catabolism bypasses the glucose-6- phosphate and fructose-6-phosphate-derived pentose phosphate pathway (PPP), which produces ribose-5-phosphate (R5P) for de novo synthesis of nucleotides and nucleic acids. The KHK product fructose-1-phosphate relieves the binding of glucokinase to GCKR, increasing glucokinase availability and promoting its translocation from sequestered nuclear to cytoplasmic localization. GCKR regulates glucokinase primarily in the liver but may play a similar role in the pancreatic islet and hypothalamus, and it has been proposed to modulate glucose sensing.
NCBI and Uniprot Product Information
NCBI Description
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]
Uniprot Description
KHK iso2: Defects in KHK are the cause of fructosuria (FRUCT). Benign defect of intermediary metabolism. Belongs to the carbohydrate kinase PfkB family. 2 isoforms of the human protein are produced by alternative splicing.
Protein type: EC 2.7.1.3; Carbohydrate Metabolism - fructose and mannose; Transferase
Chromosomal Location of Human Ortholog: 2p23.3
Cellular Component: cytoplasm; cytosol; nucleus
Molecular Function: ketohexokinase activity; ATP binding
Biological Process: carbohydrate phosphorylation; carbohydrate metabolic process; pathogenesis; fructose catabolic process
Disease: Fructosuria, Essential
Research Articles on KHK
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Product Notes
The KHK khk (Catalog #AAA389345) is a Recombinant Protein produced from E Coli and is intended for research purposes only. The product is available for immediate purchase. It is sometimes possible for the material contained within the vial of "Ketohexokinase, Recombinant Protein" to become dispersed throughout the inside of the vial, particularly around the seal of said vial, during shipment and storage. We always suggest centrifuging these vials to consolidate all of the liquid away from the lid and to the bottom of the vial prior to opening. Please be advised that certain products may require dry ice for shipping and that, if this is the case, an additional dry ice fee may also be required.Precautions
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