KHK dimer phosphorylates Fru to Fru 1-P

Stable Identifier
R-HSA-70333
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Synonyms
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
12941785 Properties of normal and mutant recombinant human ketohexokinases and implications for the pathogenesis of essential fructosuria

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

Diabetes 2003
22371574 Opposing effects of fructokinase C and A isoforms on fructose-induced metabolic syndrome in mice

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

Proc. Natl. Acad. Sci. U.S.A. 2012
19237742 Structures of alternatively spliced isoforms of human ketohexokinase

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

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

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

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

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

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

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

Hum Mol Genet 1994
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
ketohexokinase activity of KHK dimer [cytosol]
Physical Entity
Activity
This event is regulated
Negatively by
Positively by
Orthologous Events
Reviewed