Ketohexokinase (KHK)

This is a benign, asymptomatic defect of intermediary metabolism. The enzyme involved is hepatic fructokinase, also known as ketohexokinase (KHK; EC 2.7.1.3). This enzyme catalyzes the first step of metabolism of dietary fructose, conversion of fructose to fructose-1-phosphate. The KHK proteins show a high level of sequence conservation relative to rat KHK. In a well-characterized family in which 3 of 8 sibs had fructosuria, all affected individuals were found to be compound heterozygotes for 2 mutations: gly40-to-arg and ala43-to-thr. Both mutations resulted from a G-to-A transition, and each altered the same conserved region of the KHK protein. Neither mutation was seen in a sample of 52 unrelated control individuals.