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Hepatic fructokinase

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(Redirected from Ketohexokinase)
ketohexokinase (fructokinase)
Ketohexokinase homodimer, Human
Identifiers
SymbolKHK
NCBI gene3795
HGNC6315
OMIM229800
RefSeqNM_006488
UniProtP50053
Other data
EC number2.7.1.3
LocusChr. 2 p23.3-23.2
Search for
StructuresSwiss-model
DomainsInterPro
Ketohexokinase
Identifiers
EC no.2.7.1.3
CAS no.9030-50-6
Databases
BRENDAenzyme data
ExPASyNiceZyme view
KEGGenzyme entry
MetaCycmetabolic pathway
Rheareactions
PDB structuresRCSB PDB PDBe PDBsum
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PMCarticles
PubMedarticles
NCBIproteins

Hepatic fructokinase (or ketohexokinase) is an enzyme that catalyzes the phosphorylation of fructose to produce fructose-1-phosphate.

ATP + Fru    ADP + F1P
ATP + D-fructose → ADP + D-fructose-1-phosphate[1]

Isoforms

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In humans, ketohexokinase is encoded by the KHK gene, which produces two isoforms, KHK-A and KHK-C, through alternative splicing.

  • KHK-C is primarily expressed in the liver, kidney, and intestine. It has a high affinity for fructose (low Km) and is responsible for the majority of fructose metabolism.
  • KHK-A is ubiquitously expressed in many tissues at low levels. It has a significantly lower affinity for fructose (high Km) compared to the C isoform.[2]

Role in fructose metabolism

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Ketohexokinase catalyzes the first step of fructolysis by phosphorylating fructose to form fructose 1-phosphate. The resulting fructose 1-phosphate is subsequently cleaved by aldolase B, producing intermediates that enter central carbohydrate metabolism.[3]

In humans, the KHK-C isoform is responsible for most fructose metabolism in the liver, kidney, and intestine. Unlike glucose metabolism, fructose metabolism through ketohexokinase bypasses phosphofructokinase, a major regulatory step in glycolysis, allowing fructose to enter downstream metabolic pathways through fructolysis.[4]

References

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  1. Bais R, James HM, Rofe AM, Conyers RA (1985). "The purification and properties of human liver ketohexokinase. A role for ketohexokinase and fructose-bisphosphate aldolase in the metabolic production of oxalate from xylitol". Biochem. J. 230 (1): 53–60. doi:10.1042/bj2300053. PMC 1152585. PMID 2996495.
  2. Diggle CP, Shires M, Leitch D, Brooke D, Carr IM, Markham AF, Hayward BE, Asipu A, Bonthron DT (2009). "Ketohexokinase: Expression and Localization of the Principal Fructose-metabolizing Enzyme". Journal of Histochemistry & Cytochemistry. 57 (8): 763–774. doi:10.1369/jhc.2009.953190. PMC 2713076. PMID 19365088.
  3. Iizuka, Katsumi (2023). "Recent Progress on Fructose Metabolism—Chrebp, Fructolysis, and Polyol Pathway". Nutrients. 15 (7): 1778. doi:10.3390/nu15071778. PMC 10096667. PMID 37049617.
  4. Mirtschink, Peter; Jang, Cholsoon; Arany, Zoltan; Krek, Wilhelm (2018). "Fructose metabolism, cardiometabolic risk, and the epidemic of coronary artery disease". European Heart Journal. 39 (26): 2497–2505. doi:10.1093/eurheartj/ehx518. PMC 6037111. PMID 29020416.
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