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Competitive inhibition of brain hexokinase by metrizamide

Department of Medicine, Division of Neurology, University of Texas Health Science Center, San Antonio, TX.

We compared the effect of metrizamide and its parent compound glucosamine on the kinetics of dog brain hexokinase. The Michaelis constant (K_m) for glucose rose from 0.065 to 0.15 to 0.28 mM in the presence of 0, 16, and 32 mM metrizamide, respectively. For 0, 1.5, and 3.7 mM glucosamine, the K_m values were 0.065, 0.4, and 1.3 mM. No change was found in the maximal velocity with either inhibitor. Metrizamide is therefore a rather weak competitive inhibitor of brain hexokinase. However, since the brain or spinal cord may be exposed to metrizamide concentrations near 780 mM during myelography, it is predictable that glucose metabolism may be significantly impaired under these conditions. This may be the mechanism for some cases of metrizamide encephalopathy.

Address correspondence and reprint requests to Dr. Bertoni, Department of Medicine, Division of Neurology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78284.

This work was supported by a grant from the state of Texas. Dr. Bertoni is a recipient of USPHS Teacher Investigator Development Award No. K07 NS00555.

Accepted for publication August 4, 1981.