Glucose transporter protein 5 (GLUT5)

GLUT5 is a member of the facilitated glucose transporter family but is unique in its specificity for D-fructose. It acts as a passive transporter, allowing fructose to enter cells by facilitated diffusion without ATP dependence. It is most prominent on the apical surface of enterocytes in the small intestine and other metabolic tissues. Dysregulation of GLUT5 is implicated in fructose malabsorption (leading to gastrointestinal symptoms), obesity, diabetes, and certain cancers where GLUT5 is overexpressed to support increased energy demands. Structurally, GLUT5 belongs to the Major Facilitator Superfamily (MFS), and its transport mechanism involves alternating conformational changes that open and close to each side of the membrane, coordinated by substrate-induced gating. The molecular determinants for fructose binding involve specific hydrogen-bonding residues within the transmembrane domains, distinguishing it from other GLUT isoforms that transport glucose. GLUT5 is a validated therapeutic target, and several efforts focus on developing selective inhibitors, although clinical translation faces challenges due to potential cross-reactivity with other GLUTs and widespread physiological roles in fructose metabolism. Overexpression of GLUT5 can serve as a diagnostic or prognostic marker particularly in digestive system disorders and metabolic tumors.

Other names

Sugar transporter protein GLUT5Glucose transporter 5Solute carrier family 2 member 5SLC2A5

Inhibition of fructose transport via competitive or allosteric binding that blocks the substrate (fructose) entry or conformational transition of GLUT5