{"entity":{"id":"glut-hexokinase","kind":"target","name":"GLUT1 / hexokinase (glucose metabolism)","aka":["GLUT1","SLC2A1","hexokinase II","HK2"],"tldr":"The two-step system cells use to pull in and lock up glucose for energy. Many cancers rely on this system much more heavily than normal tissue, and a radioactive sugar look-alike called FDG exploits it to light up tumours on a PET scan.","summary":"Glucose enters cells through facilitative glucose transporters (GLUTs), of which GLUT1 is the most widely distributed, and is then immediately phosphorylated by hexokinase (chiefly hexokinase II, HK2, in tumours) to glucose-6-phosphate, trapping it inside the cell for glycolysis. Malignant cells characteristically upregulate both GLUT1 and HK2 to sustain the Warburg effect - a high rate of glycolysis even when oxygen is available, driven by oncogenic signalling (PI3K/AKT, MYC, RAS, loss of p53) and by hypoxia acting through HIF-1α, which transcriptionally activates GLUT1 and glycolytic enzymes.\n\n18F-fludeoxyglucose (FDG) is a glucose analogue that is carried into cells by GLUT1 (and GLUT3) exactly as glucose is, and phosphorylated by hexokinase to FDG-6-phosphate; because this metabolite lacks the 2'-hydroxyl group needed for further glycolytic processing and most tumours have low glucose-6-phosphatase activity to reverse the reaction, FDG-6-phosphate becomes metabolically trapped and accumulates in proportion to glycolytic flux. This is read out on PET as the standardised uptake value (SUV), the basis of FDG-PET staging, restaging and treatment response assessment across most solid tumours and lymphomas.\n\nAs a target, GLUT1/hexokinase's strength is near-universal upregulation across a very wide range of cancers, giving FDG-PET its broad utility as a single default oncology tracer. Its central weakness is specificity: any tissue with high glucose demand - brain, myocardium, active skeletal muscle, brown fat, healing wounds, infection and inflammation - also accumulates FDG strongly, so a positive scan requires anatomical and clinical correlation rather than being cancer-specific by itself; hyperglycaemia at the time of injection also competes with FDG uptake and reduces sensitivity.","asOf":"2026-09-22","links":[{"label":"PMC: roles of GLUT-1 and HK-II expression in tumour biology and FDG uptake","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6508962/"},{"label":"PMC: mechanisms underlying FDG uptake in cancer","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5120247/"},{"label":"StatPearls: fludeoxyglucose (18F) mechanism of action","url":"https://www.ncbi.nlm.nih.gov/books/NBK557653/"},{"label":"PMC: imaging cancer metabolism, underlying biology and pitfalls of FDG-PET","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6126440/"}],"tags":["metabolism","glycolysis","pan-cancer"],"related":["fludeoxyglucose-f18","fdg-pet","suv","f-18"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"SLC2A1","biology":"Glucose enters cells through facilitative glucose transporters (chiefly GLUT1) and is then phosphorylated by hexokinase (chiefly hexokinase II in tumours), trapping it inside the cell. Cancer cells characteristically upregulate both proteins to sustain high glycolytic flux even in the presence of oxygen (the Warburg effect), which is what the glucose analogue FDG exploits for PET imaging.","whereFound":["Most solid tumours and lymphomas: GLUT1 and hexokinase II upregulated in proportion to glycolytic rate, the basis of FDG-PET","Brain (grey matter), myocardium, active skeletal muscle, brown adipose tissue: high physiological glucose uptake, a source of false-positive or confounding FDG signal","Sites of infection and inflammation: activated leukocytes also take up FDG avidly, another source of non-specific uptake"],"targetClass":"enzyme","prevalence":[]},"route":"/targets/glut-hexokinase/","neighbours":{"drug":[{"id":"fludeoxyglucose-f18","kind":"drug","name":"Fludeoxyglucose F-18 (FDG)","route":"/drugs/fludeoxyglucose-f18/"}],"technology":[{"id":"fdg-pet","kind":"technology","name":"FDG PET","route":"/technologies/fdg-pet/"}],"term":[{"id":"suv","kind":"term","name":"Standardised uptake value (SUV)","route":"/terms/suv/"}],"isotope":[{"id":"f-18","kind":"isotope","name":"Fluorine-18","route":"/isotopes/f-18/"}],"indication":[{"id":"nsclc","kind":"indication","name":"Non-small cell lung cancer","route":"/indications/nsclc/"}]}}