Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.1 (hexokinase)
 5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two cases of absence status are described, one case following metrizamide myelography and the other from omnipaque myelography. Metrizamide has been well known to cause convulsive seizures even in patients without epilepsy. The exact mechanism is not known but appears to be direct neuronal toxic effects possibly due to competitive inhibition of hexokinase activity. The acute confusional state following myelography from water soluble agents is reviewed. In view of the difficulty in clinical diagnosis and the excellent response to anticonvulsant therapy, the possibility of this clinical entity should be specifically excluded by EEG in any person suffering from prolonged confusion following myelography with water soluble agents.
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PMID:Absence status epilepticus resulting from metrizamide and omnipaque myelography. 339 4

Metrizamide neurotoxicity has been hypothesized to be caused by an inhibitory effect of the drug on glucose metabolism. Metrizamide contains a glucose side chain, and glucose analogues including metrizamide have been shown to be inhibitors of hexokinase, an enzyme that is central to cerebral glucose metabolism. We studied the effect of the nonionic contrast agents iohexol, iotrol, and iopamidol, and the ionic contrast meglumine diatrizoate, on hexokinase in vitro. Although metrizamide reproducibly caused competitive inhibition of the reaction, the nonglucose contrast agents had no significant effect on the enzyme. These results add further support for the glucose hypothesis of metrizamide neurotoxicity.
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PMID:Further support for the glucose hypothesis of metrizamide toxicity. The effect of metrizamide and glucose analogue-free contrast media on hexokinase. 355 85

We have compared the competitive inhibitory effects of 2-deoxyglucose, glucosamine, N-acetylglucosamine, N-benzoylglucosamine, and the commonly used radiographic and density gradient agent metrizamide (2-[3-acetamido-2,4,6-triiodo-5-(N-methylacetamido) benzamido]-2-deoxyglucose) on the mitochondrial and soluble forms of human brain hexokinase. Metrizamide produces a classical competitive inhibition with glucose for human brain hexokinase, with Kis of 2.8 and 2.5 mM, respectively, for the mitochondrial and soluble forms. Glucosamine exhibited Kis of 0.58 and 0.29 mM, while 2-deoxyglucose exhibited Kis of 0.074 and 0.15 mM and N-acetylglucosamine 0.098 and 0.092 mM for these two forms, respectively. N-Benzoylglucosamine was by far the most effective inhibitor tested, with Ki values of 0.0086 and 0.022 mM, respectively. In order of increasing potency as a competitive inhibitor for mitochondrial hexokinase are metrizamide, glucosamine, N-acetylglucosamine, 2-deoxyglucose, and N-benzoylglucosamine. For the soluble form of the enzyme in increasing potency are metrizamide, glucosamine, 2-deoxyglucose, N-acetylglucosamine, and N-benzoylglucosamine. Since N-benzoylglucosamine was over 100 times more potent than metrizamide, some of the effects of metrizamide could be due to contamination by N-benzoylglucosamine. However, gas chromatography-mass spectrometry analysis of metrizamide did not indicate the presence of N-benzoyl-glucosamine. In addition, column chromatographic separation of commercially available metrizamide and reconstitution of freeze-dried eluate fractions localized the inhibitory effect to the metrizamide peak.
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PMID:Competitive inhibition of human brain hexokinase by metrizamide and related compounds. 669 84

We compared the effect of metrizamide and its parent compound glucosamine on the kinetics of dog brain hexokinase. The Michaelis constant (Km) 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 Km 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.
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PMID:Competitive inhibition of brain hexokinase by metrizamide. 719 50

Marked asterixis occurred in two patients following metrizamide myelography. One also suffered generalized seizures and the other had severe stuttering speech for seven days. The spectrum of toxic manifestations of metrizamide is reviewed with emphasis on the unusual lethargy and other depressive effects seen with this relatively safe agent. The hypothesis that metrizamide exerts a ouabain-like effect on the cortical surface was tested. Metrizamide in concentrations as high as 20 mM had no inhibitory effect on rat cerebral K+-para-nitrophenylphosphatase, a partial reaction of (Na+K+)-adenosine triphosphatase. Because metrizamide is a 2-deoxyglucose analogue, a competitive inhibition of hexokinase at the first step in glycolysis was also postulated. Metrizamide was found to competitively inhibit commercial (microbial) hexokinase. The Michaelis constant for glucose rises from 0.13 to 0.25 to 0.33 to 0.91 mM in the presence of 0, 0.4, 1.0, and 2.0 mM metrizamide, respectively. Since the concentration of metrizamide over the cerebral cortex after routine myelography may be approximately 50 mM compared with a glucose concentration of only 3.6 mM (65 mg/dl), it is postulated that impaired brain glucose metabolism may be responsible for some of the toxic effects of metrizamide.
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PMID:Asterixis and encephalopathy following metrizamide myelography: investigations into possible mechanisms and review of the literature. 722 1

A case of Iotrolan encephalopathy is reported. A 66-year-old woman, suffering from subarachnoid hemorrhage, was admitted to our department on January 17th, 1995. After an operation for aneurysmal clipping and ventriculo-peritoneal shunt, she was discharged with no neurological deficiency. CT scan revealed ventricular enlargement and slight periventricular lucency. She was re-admitted on January 4th, 1996. She was suffering from nausea, vomiting, right hemiparesis, right hemi-hypesthesia and disturbance of consciousness. CT scan demonstrated right thalamic bleeding and bilateral ventricular hemorrhage. Further ventricular enlargement was also revealed. With medical treatment, her symptoms were relieved gradually. But disorientation and memory disturbance continued. Shuntography with Iotrolan was performed on February 2nd, 1996. The ventriculo-peritoneal shunt was demonstrated to be occluded on the abdominal side. The volume of Iotrolan used was about 8cc. She became very restless on the night of the examination. Her temperature was up to 38. CT on February 4th demonstrated brain penetration of the Iotrolan. Revision of ventriculo-peritoneal shunt, administration of steroids and hydration was performed. CSF findings demonstrated no abnormalities. Her symptoms were relieved gradually. Iotrolan is a non-ionic contrast media of dimer type, composed of C37 H48 I6 N6 O18. Its distinctive features are low distributing coefficient and high affinity with water. Contrasting several reports of Metrizamide encephalopathy, only 2 cases of Iotrolan encephalopathy were reported. Iotrolan is reported to be much safer than Metrizamide. We were able to find brain penetration by Iotrolan. It is expected to be a characteristic radiological finding of encephalopathy induced by contrast media. The mechanism of Iotrolan encephalopathy is obscure. Several theories concerning Metrizamide encephalopathy are proposed. These are (1) inhibition of hexokinase, (2) inhibition of acethylcholinesterase, (3) immunological mechanism and (4) vascular disturbance. Iotrolan has no 2-deoxy-glucose structure. The inhibition theory of hexokinase is least expected. Related matters are circulatory disturbance of liquor, dehydration, excessive contrast media, advanced age, diabetes mellitus, hypertension, epileptic patients and patients taking phenothiazines. Prompt therapy is important. Removal of contrast media, hydration and administration of steroids should be performed as early as possible.
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PMID:[A case of Iotrolan encephalopathy]. 893 76