Ketohexokinase(KHK),the rate-limiting enzyme in the first step of fructose metabolism,exists in two alternatively spliced isoforms of ketohexokinase C(KHK-C)and ketohexokinase A(KHK-A).KHK-C is the main undertaker of fructose catabolism,and through its protein acetylation,fructose metabolites are more used in the synthesis of triglycerides,which is the root cause of fructose-related metabolic diseases.Moreover,KHK also plays an important role in the growth,proliferation and metastasis of many different types of cancers.KHK-C triggers a reprogrammed transcriptional and metabolic profile,while KHK-A acts as a serine or threonine protein kinase,phosphorylating and activating different signaling molecules or some rate-limiting enzyme to facilitate tumor growth,proliferation and metastasis.This article reviews the structure,distribution,regulation,function,and correlation with clinical diseases of KHK,in order to provide a theoretical foundation for further researches.
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