Defective KHK does not phosphorylate beta-D-fructose

Stable Identifier
Reaction [transition]
Homo sapiens
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Variant KHK (ketohexokinase) protein fails to catalyze the phosphorylation of fructose to yield fructose 1-phosphate (Fru 1-P), the first step of fructose catabolism in the liver. This defect is associated with essential fructosuria, a rare benign condition characterized by elevated urinary fructose levels associated with consumption of fructose. Two missense mutant alleles have been identified in DNA sequencing studies of affected individuals (Bouthron et al. 1994). One, G40R, has no detectable activity. The second, A43T, encodes a protein whose liver ("A") isoform is inactive but whose peripheral ("C") isoform, though thermally unstable, retains some activity (Asipu et al. 2003).

Literature References
PubMed ID Title Journal Year
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
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 mutant dimers [cytosol]

Normal reaction
Functional status

Loss of function of KHK mutant dimers [cytosol]

Name Identifier Synonyms
carbohydrate metabolic disorder DOID:2978 disorder of carbohydrate transport and metabolism, inborn errors of carbohydrate metabolism, inborn carbohydrate metabolism disorder
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