COMPETITIVE-INHIBITION OF RAT-BRAIN HEXOKINASE BY 2-DEOXYGLUCOSE, GLUCOSAMINE, AND METRIZAMIDE

Effects of metrizamide on the kinetics of rat brain hexokinase were compared in vitro with those of 2-deoxyglucose and glucosamine. Although metrizamide, 2-deoxyglucose and glucosamine are competitive inhibitors of approximately equal potency for glucose of yeast hexokinase (Ki .apprx. 0.7 mM for all 3), metrizamide is a much weaker competitive inhibitor (Ki .apprx. 20 mM) of rat brain hexokinase than either 2-deoxyglucose or glucosamine (Ki .apprx. 0.3 mM for both). This indicates a greater active site specificity of rat brain hexokinase than of yeast hexokinase. Rat brain hexokinase activity is enhanced .apprx. 3-fold in the presence of 0.05, 0.2 and 0.8 mg/ml bovine serum albumin, while yeast hexokinase is only enhanced by 50% under these conditions. Despite the high Ki value for metrizamide, interference with glucose metabolism may occur whenever metrizamide is present in much higher concentrations than glucose. Myelography in humans is one such situation.