Glucose transporter 3 (GLUT3), encoded by SLC2A3 gene is a glucose transporter, specifically expressed in neurons.

GLUT3 is a uniporter carrier, it binds one molecule of substrate at a time and transports it across the membrane. Transport occurs down the substrate concentration gradient, thereby allowing a constant supply of blood sugar for cell’s metabolism. The substrate binding site of GLUT3 is alternatively accessible from either side of the membrane by conformational changes of the protein. Thus, it enables both intake and export of glucose, according to glucose levels in and out of the cell¹.

In the context of cancer, tumor cells often increase their glucose consumption and lactate production. An increasing number of studies are identifying GLUT3 and GLUT1 as major participants in the accelerated metabolism demonstrated by cancer cells. GLUT3 and GLUT1 are also overexpressed in several types of cancer tumors and hence, efforts toward the elucidation of the structure and function of glucose transporters as targets for diagnosis and new cancer therapeutics are invested².

GLUT3 shares a conserved fold that is made of two domains, N- and C-terminal, and six trans-membrane spanning α-helices each. The N- and C-terminal domains are connected by a third domain, comprising five short intracellular α-helices. The overall protein structure has roughly the shape of the letter “V”, with a cavity opened towards the extracellular side of the membrane that allows glucose to reach and bind to the substrate binding site^3,4.