5. (a)Hexokinase IV is known as glucokinase (GCK) and is a central metabolic enzyme thatparticipates in glucose homeostatic maintenance by governing the rates of glucose catabolism in pan-creatic B-cells and glycogen storage in hepatocytes (liver cells). In contrast to the regulatory mecha-nisms of hexokinase I or Il in other tissues, GCK is regulated by binding to the Glucokinase RegulatoryProtein (GRP) located in the cell nucleus. When glucose in hepatocytes is low, GCK is sequestered inthe nucleus by binding to the GRP. High glucose, for instance, after ingestion of a meal, disrupts theGRP-GCK complex, allowing the GCK to diffuse into the cytoplasm to convert glucose into glucose-6-phosphate. Contrast the properties of hexokinases I and IV with respect to oligomeric structure, mech-anism of regulation of their activity, KM value, and dependence of catalytic activity on cellular location.Hexokinase I is found in, for instance, muscle tissue.Propertysubunit structutrehexokinase I/IIhexokinase IVmechanism of regulationKM valuecellular locationCF3FoHCF3(b) Diabetes mellitus is a disease characterizedby reduced sensitivity of cellular membranes ofmuscle and adipose tissue to insulin facilitatinguptake of glucose. The resultant effect is thatglucose in the blood stream rises to higher lev-els and decreases more slowly than in unaf-fected individuals. Recently a synthetic pipera- H2Nzine derivative, Compound Y, shown on theright, has been shown to function by causing dis-sociation of the GRP-GCK complex. Administra-tion of Compound Y.to diabetic rats after feed-ing had the effect shown by the graph on theright.O.s-NNNCompound Y500Legend for sym-bols: •, vehicle;V, Cmpd Y; O,GCK activator; x,metformin (awidely prescribeddrug used to treatdiabetes melli-400.300-******200-***(b1)formulas (except for nucleotides, etc.) catalyzedby hexokinase IV or glucokinase.Write the reaction using structural100-***47Time after dose (h)Blood glucose (mg dl-1)

Hexokinases: An enzyme that phosphorylates hexoses (six-carbon sugars) to produce hexose phosphate.…

5. (a) Hexokinase IV is known as glucokinase (GCK) and is a central metabolic enzyme that participates in glucose homeostatic maintenance by governing the rates of glucose catabolism in pan- creatic ß-cells and glycogen storage in hepatocytes (liver cells). In contrast to the regulatory mecha- nisms of hexokinase I or II in other tissues, GCK is regulated by binding to the Glucokinase Regulatory Protein (GRP) located in the cell nucleus. When glucose in hepatocytes is low, GCK is sequestered in the nucleus by binding to the GRP. High glucose, for instance, after ingestion of a meal, disrupts the GRP-GCK complex, allowing the GCK to diffuse into the cytoplasm to convert glucose into glucose-6- phosphate. Contrast the properties of hexokinases I and IV with respect to oligomeric structure, mech- anism of regulation of their activity, KM value, and dependence of catalytic activity on cellular location. Hexokinase I is found in, for instance, muscle tissue. Property subunit structutre mechanism of regulation KM value cellular location hexokinase I/II (b) Diabetes mellitus is a disease characterized by reduced sensitivity of cellular membranes of muscle and adipose tissue to insulin facilitating uptake of glucose. The resultant effect is that glucose in the blood stream rises to higher lev- els and decreases more slowly than in unaf- fected individuals. Recently a synthetic pipera- H₂N zine derivative, Compound Y, shown on the right, has been shown to function by causing dis- sociation of the GRP-GCK complex. Administra- tion of Compound Y.to diabetic rats after feed- ing had the effect shown by the graph on the right. (b1) Write the reaction using structural formulas (except for nucleotides, etc.) catalyzed by hexokinase IV or glucokinase. N Legend for sym- bols:, vehicle; V, Cmpd Y; , GCK activator; x, metformin (a widely prescribed drug used to treat diabetes melli- Blood glucose (mg dl-¹) 500 400- 300- 200- 100- hexokinase IV 0 Compound Y *** *** CF3 кон CF3 *** 4 Time after dose (h) *** 7