Sandbox 172: Difference between revisions

Hexokinase Type I functions in a mainly catabolic role; it is responsible for introducing glucose the glycolytic process in attempts to produce ATP. Hexokinase Type I phosphorylates a hexose into a hexose phosphate; most commonly the substrate of hexokinase I is found to be glucose and the product found to be glucose-6-phosphate.<ref>Bianchi M., Casabianca A., Magnani M., Serafini G., Stocchi V. Human hexokinase type I microheterogeneity is due to different amino-terminal sequences. The Journal of Biological Chemistry. 1991. '''266''': 502-505.</ref> Mammalian brain tissue shows a high content of Hexokinase Type I which reiterates the idea that this isoenzyme is needed to maintain high rates of energy metabolism. Hexokinase Type I associated with brain homogenates demonstration an interaction with outer mitochondrial membrane. The binding of to this mitochondria is highly dependent on the N-terminus sequence. The protein porin is then responsible for the formation of a channel in which metabolites can pass through the mitochondrial membrame.<ref>Wilson, J. Isozymes of mammalian hexokinase: structure, subcellular localization and metabolic function. The Journal of Experimental Biology. 2003.'''206''':2049-2057.</ref>

Entry of glucose into a cell is highly dependent on the number of glucose transporters present on the cell surface and the affinity that these specific transporters have for glucose. Expression of these glucose transporter members vary in level and strength different from tissue to tissue. Hexokinase type I has a low Km and therefore a high affinity for glucose. This allows the initiation of glycolysis even when blood glucose levels are relatively low. The inhibition of hexokinase type I is caused by its product, glucose-6-phosphate. This inhibitory step prevents over-consumption of cellular ATP when glucose is not limiting.  

The activity of hexokinase type I becomes inihibited when glucose-6-phosphate binds to the inactive, N-terminal half of the enzyme. This binding stimulates the inhibition of the active, C-terminal half and as a result, the catalysis of glycolysis becomes stagnant. The presence of orthophosphate relieves the product inhibition by displacing the bound glucose-6-phosphate and binding to the enzyme itself. The N-terminal half then responds differently to the newly bound orthophosphate and evokes an active reaction from the C-terminal half. The ability of the C-terminal half to significantly different between the two possible binding molecules is evident by the presence of ADP-ligated active sites on the hexokinase type I enzyme as well as ADP binding sites on the N-terminal halves.<ref name="two" />