D-fructose (Fru)

D-fructose is a simple ketonic monosaccharide found in many plants, where it is often bonded to glucose to form the disaccharide sucrose. It is one of the three dietary monosaccharides, along with glucose and galactose, that are absorbed directly into the blood during digestion [1]. In the human body, fructose is primarily metabolized in the liver via the fructolysis pathway, where it is converted into fructose-1-phosphate by the enzyme ketohexokinase [2]. Because this pathway bypasses the major rate-limiting step of glycolysis, high fructose intake can lead to an overproduction of uric acid and increased de novo lipogenesis, contributing to metabolic disorders [3]. While D-fructose is a metabolite rather than a therapeutic target protein, its metabolic pathways are central to the pathology of obesity, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD) [4]. Consequently, therapeutic efforts focus on inhibiting the enzymes and transporters responsible for its uptake and processing, such as GLUT5 and ketohexokinase [5]. Sources: [1] PubChem (CID 5793) [2] StatPearls: Biochemistry, Fructose Metabolism [3] Tappy L, Lê KA. "Metabolic effects of fructose and the worldwide increase in obesity." Physiol Rev. 2010. [4] Jensen T, et al. "Fructose and sugar: A major mediator of non-alcoholic fatty liver disease." J Hepatol. 2018. [5] Maryanoff BE. "Inhibitors of Ketohexokinase: Potential New Drugs for the Treatment of Metabolic Diseases." J Med Chem. 2020.

Other names

LevuloseFruit sugarD-fructofuranoseD-fructopyranose(3S,4R,5R)-1,3,4,5,6-pentahydroxyhexan-2-one

Pharmacological intervention typically involves the inhibition of ketohexokinase (KHK) to block the initial step of fructose metabolism or the inhibition of the GLUT5 transporter to reduce intestinal absorption.