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)

The interconnections between EEG, intermediary and energy metabolism of the brain cortex and CSF potassium level are studied during severe hypercapnia in anaesthetized, artificially ventilated cats. Hypercapnic animals were ventilated with 40 to 50% to CO2 in oxygen. During severe hypercapnia the EEG becomes isoelectric. The CSF potassium concentration is raised and the changes in metabolism suggest an acidosis-induced inhibition of phosphofructokinase and, probably, of hexokinase. The energy charge potential remains unchanged whereas the cortical ATP concentration increases slightly. It is assumed that the changes in P-creatine and creatine levels are related to the pH-dependency of creatine phosphokinase. Recovery animals were ventilated with 40% CO2 in O2 and subsequently with room air. After termination of CO2 inhalation the EEG reappears, the CSF potassium concentration normalizes, and the inhibition of the glycolytic enzymes disappears. The energy charge potential shows a small decrease. It is not possible to trace back the disappearance of the EEG to only one of the recorded parameters. Cortical P-creatine levels, CSF potassium concentration, changes in membrane permeability and cortical amino acid concentrations are considered in this context.
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PMID:Influence of severe hypercapnia upon cerebral cortical metabolism, CSF electrolyte concentrations and EEG in the cat. 13 59

Mechanisms contributing to the rare but consistent neurotoxicity of contrast media currently in clinical use for the radiological examination of the subarachnoid space remain to be isolated. We assessed, by means of the (14C)-2-deoxy-D-glucose (2-DG) autoradiographic method, the effect of three non-ionic, low-osmolar contrast media, namely metrizamide, iopamidol and iohexol, on the local cerebral glucose utilization in the rat brain after intracisternal application. A significant (-30%) global reduction of the brain's metabolic activity occurred following intracisternal metrizamide injection. When compared with the mock-CSF control group the greater relative changes were observed in the supratentorial grey matter structures. In contrast, no significant changes were observed in metabolic brain activity in rats treated intracisternally with iopamidol and iohexol. These findings were consistent with the hypothesis that metrizamide is a competitive inhibitor of human brain hexokinase. The apparent lack of interference on neural tissue metabolism makes the second generation contrast media less neurotoxic and more suitable for neuroradiological subarachnoid investigations in clinical settings. The present experimental work establishes the 2-DG method as a viable laboratory approach to investigate aspects of neuronal dysfunction induced by contrast media.
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PMID:Effect of injections of contrast media on regional uptake of (14C)-2-deoxyglucose by the rat brain. 229 3

The myelographic contrast agent, metrizamide, causes a temporary confusional state in many patients. Since metrizamide is a 2-deoxyglucose analogue, it was tested for inhibitory effects on glucose metabolism. The Michaelis constant (Km) of human brain hexokinase for glucose rose from 0.039 to 0.24 and 0.47 mM with final metrizamide concentrations of 0, 16 and 32 mM, respectively. The maximal velocity did not change. Since metrizamide is injected into the human CSF in concentrations of up to 780 mM, impairment of brain glucose metabolism can be expected. These effects could be largely counteracted if metrizamide were injected in a 100 mM glucose solution.
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PMID:Metrizamide inhibits human brain hexokinase. 720 85

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

It has recently been proposed that hypothalamic glial cells sense glucose levels and release lactate as a signal to activate adjacent neurons. GK (glucokinase), the hexokinase involved in glucose sensing in pancreatic beta-cells, is also expressed in the hypothalamus. However, it has not been clearly determined if glial and/or neuronal cells express this protein. Interestingly, tanycytes, the glia that cover the ventricular walls of the hypothalamus, are in contact with CSF (cerebrospinal fluid), the capillaries of the arcuate nucleus and adjacent neurons; this would be expected for a system that can detect and communicate changes in glucose concentration. Here, we demonstrated by Western-blot analysis, QRT-PCR [quantitative RT-PCR (reverse transcription-PCR)] and in situ hybridization that GK is expressed in tanycytes. Confocal microscopy and immuno-ultrastructural analysis revealed that GK is localized in the nucleus and cytoplasm of beta1-tanycytes. Furthermore, GK expression increased in these cells during the second week of post-natal development. Based on this evidence, we propose that tanycytes mediate, at least in part, the mechanism by which the hypothalamus detects changes in glucose concentrations.
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PMID:Glial glucokinase expression in adult and post-natal development of the hypothalamic region. 2053 73