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Hexokinase is a transferase protein. It is the first enzyme in the glycolytic pathway that converts glucose into glucose-6-phosphate. This enzyme uses ATP to phosphorylate the 6-hydroxyl group of glucose, which is inhibited by its product, glucose-6-phosphate. It is also allosterically relieved of product inhibition by the addition of phosphate. Hexokinase controls the flow of glucose into energy metabolism in many mammalian tissues, such as blood cells, and brain tissue. Glucose-6-phosphate and glucose bind synergistically to hexokinase, as well as glucose and phosphate. This phosphate however plays a small role in the regulation of hexokinase during respiration. This is because gylcolysis is limited by the supply of glucose. During times of oxygen deprivation more ATP must come from glycolysis. This is because pyruvate forms lactic acid instead of entering the Kerb's cycle. As ATP phosphorylates glucose to glucose-6-phosphate, it increases its Gibbs free energy from -31 KJ to 14.3 KJ. This makes the reaction thermodynamically favorable. <ref> Worthingtin K. Hexokinase. Worthington Biochemical Corporation.2011; I.U.B.:2.7.1.1. [http://www.worthington-biochem.com/HK/default.html]</ref>

The active site residues for Hexokinase are Asp205, Lys169, Asn204, Glu256,and Thr168. <ref> Koshland D. Induced Fit and Hexokinase.Fig.7 Active Site of Glucokinase/Hexokinase.2010; [http://www.chem.ucsb.edu/~molvisual/ABLE/induced_fit/index.html] </ref> These residues are located in the deep cleft at the interface between the two lobes. This active site is cable of bonding two ligands, glucose, and glucose-6-phosphate. Hexokinase undergoes an induced fit conformational change when glucose binds. This conformational change prevents the hydrolysis of ATP, and is allosterically inhibited by physiological concentrations of glucose-6-phosphate the product. Hexokinase has two conformational states. The open state occurs prior to glucose binding. ATP is bound to the large lobe, but is far away from the glucose binding site, and in a different position than it assumes in the active site. When the glucose binds to Hexokinase a large conformational change occurs. This change closes the two lobes around the glucose substrate. This conformational state is referred to as the closed state. <ref> Kitto B.G, Caras J., Caras P. Interactive Concepts in Biochemistry. Structural Tutorials.2008; Chp: 15.1, 15.5. [ http://higheredbcs.wiley.com/legacy/college/boyer/0471661791/structure/hexokinase/hexokinase.htm] </ref>