KHK dimer phosphorylates Fru to Fru 1-P

Stable Identifier
Reaction [transition]
Homo sapiens
ATP + beta-D-fructose => ADP + beta-D-fructose 1-phosphate + H(+), Ketohexokinase (KHK) phosphorylates beta-D-fructose to form fructose 1-phosphate, ATP + beta-D-fructose => ADP + D-fructose 1-phosphate
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Cytosolic ketohexokinase (KHK, also known as fructokinase) catalyzes the reaction of D-fructose (Fru) and ATP to form D-fructose 1-phosphate (Fru 1-P) and ADP. Two isoforms of the enzyme, A and C, are encoded by alternatively spliced forms of the gene; both form catalytically active dimers. The C isoform is predominant in liver and kidney tissues, has high affinity for fructose, and is probably responsible for the bulk of fructose phosphorylation in vivo (Asipu et al. 2003; Trinh et al. 2009). The A isoform is found in lower levels in many other tissues and may serve a role in fructose metabolism outside of liver and kidney (Funari et al. 2005). The physiological role of KHK has been established from metabolic and DNA sequencing studies of patients with essential fructosuria (Bonthron et al. 1994) and in mouse models for this disease (Diggle et al. 2010; Ishimoto et al. 2012).

Literature References
PubMed ID Title Journal Year
22371574 Opposing effects of fructokinase C and A isoforms on fructose-induced metabolic syndrome in mice

Maruyama, S, Diggle, CP, Ishimoto, T, Asipu, A, Kosugi, T, Bonthron, DT, Roncal-Jimenez, CA, Jackman, MR, Sautin, YY, Sánchez-Lozada, LG, Rodriguez-Iturbe, B, Garcia, GE, Rivard, CJ, Maclean, PS, Johnson, RJ, Le, MT, Lanaspa, MA

Proc. Natl. Acad. Sci. U.S.A. 2012
12941785 Properties of normal and mutant recombinant human ketohexokinases and implications for the pathogenesis of essential fructosuria

Hayward, BE, O'Reilly, J, Asipu, A, Bonthron, DT

Diabetes 2003
19237742 Structures of alternatively spliced isoforms of human ketohexokinase

Trinh, CH, Phillips, SE, Asipu, A, Bonthron, DT

Acta Crystallogr D Biol Crystallogr 2009
16266770 Genes required for fructose metabolism are expressed in Purkinje cells in the cerebellum

Freeman, D, Funari, VA, Tolan, DR, Herrera, VL

Brain Res. Mol. Brain Res. 2005
20841500 Both isoforms of ketohexokinase are dispensable for normal growth and development

McRae, C, Markham, AF, Hayward, BE, Crellin, D, Diggle, CP, Fisher, J, Asipu, A, Carr, IM, Shires, M, Bonthron, DT

Physiol. Genomics 2010
7833921 Molecular basis of essential fructosuria: molecular cloning and mutational analysis of human ketohexokinase (fructokinase)

Donaldson, IA, Brady, N, Steinmann, B, Bonthron, DT

Hum Mol Genet 1994
Catalyst Activity

ketohexokinase activity of KHK dimer [cytosol]

This event is regulated
Negatively by