1 3 DOI 10.1007/s00726-017-2417-2 Amino Acids REVIEW ARTICLE Glucose transportation in the brain and its impairment in Huntington disease: one more shade of the energetic metabolism failure? Veronica Morea 1 · Eris Bidollari 2,3 · Gianni Colotti 1 · Annarita Fiorillo 1 · Jessica Rosati 3 · Lidia De Filippis 3 · Ferdinando Squitieri 4 · Andrea Ilari 1 Received: 9 March 2017 / Accepted: 1 April 2017 © Springer-Verlag Wien 2017 processes are impaired in HD, and discuss the potential ability of strategies aimed at increasing intracellular energy levels to counteract neurological and motor degeneration in HD patients. Keywords Huntington disease · Energetic metabolism · Glucose transport · GLUT1 · GLUT3 Brain glucose metabolism The brain relies predominantly on glucose as a substrate for its metabolism, at variance with other body tissues that can utilize other energy sources, mostly fatty acids. Brain requirements for glucose are quite high: the adult brain weighs ~2% of the whole body, but consumes ~20% of total body glucose in the resting state (Mergenthaler et al. 2013). Glucose is used by the brain to both provide the energy for cellular functions (e.g., generation of synaptic and action potentials, maintenance of ion gradients, etc.) and as a carbon source for the biosynthesis of a variety of molecules (e.g., neurotransmitters) (Siegel et al. 1999). In brain cells glucose is phosphorylated by hexokinase (HK) to glucose-6-phosphate (G6P) (Patel et al. 2014) and metabolized, as in other cells, through one of the following pathways. 1. Glycolysis. It takes place in the cytoplasm under anaerobic conditions, and leads to formation, for each glucose molecule, of two molecules of pyruvate, two molecules of adenosine triphosphate (ATP) and two molecules of NADPH. NADPH is a reducing agent, important for the management of oxidative stress, which in animals is mostly produced by the pentose phosphate pathway (see below). ATP stores chemical Abstract Huntington’s disease (HD) or Huntington’s cho- rea is the most common inherited, dominantly transmitted, neurodegenerative disorder. It is caused by increased CAG repeats number in the gene coding for huntingtin (Htt) and characterized by motor, behaviour and psychiatric symp- toms, ultimately leading to death. HD patients also exhibit alterations in glucose and energetic metabolism, which result in pronounced weight loss despite sustained calorie intake. Glucose metabolism decreases in the striatum of all the subjects with mutated Htt, but affects symptom presen- tation only when it drops below a specific threshold. Recent evidence points at defects in glucose uptake by the brain, and especially by neurons, as a relevant component of central glucose hypometabolism in HD patients. Here we review the main features of glucose metabolism and trans- port in the brain in physiological conditions and how these Veronica Morea and Eris Bidollari contributed equally to the work. * Ferdinando Squitieri f.squitieri@css-mendel.it * Andrea Ilari andrea.ilari@uniroma1.it 1 National Research Council of Italy (CNR), Institute of Molecular Biology and Pathology c/o Department of Biochemical Sciences, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy 2 Department of Biochemical Sciences, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy 3 IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy 4 Huntington and Rare Diseases Unit, IRCCS Casa Sollievo della Sofferenza Hospital c/o Mendel Institute of Human Genetics, Viale Regina Margherita, 00198 Rome, Italy