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)

To what extent can damage to the central and peripheral nervous systems be ascribed to chronic aluminum (Al) intoxication taken as a chelating agent for phosphorus, to limit hyperphosphatemia in uremic patients? Since Al is normally eliminated by the renal route, its accumulation in uremia has to be ascribed to a reduced or abolished renal clearance of the metal, which results in preferential toxicity for certain tissues, especially nervous tissue, which shows difficulty in eliminating Al, even after intake has been stopped. This review discusses, on the basis of toxicologic, experimental and clinical data, the possible pathogenic steps of Al neurotoxicity in uremia, considering: the damage to axonal transport in which Al intoxication tends to affect the components of the cytoskeleton, the polymerization phase of the alpha and beta tubulin constituents of neurotubules, and the normal translocation of neurofilaments from the perikaryon to more distal positions of the axon; the abnormalities in the brain pool of adrenergic, cholinergic and GABA neurotransmitters; the increase in permeability and changes in perm-selectivity of the blood-brain-barrier, with further loss of neurotransmitters and with acquisition, from the systemic circulation, of neurotransmitter-like substances such as hormones, monoamines and peptides, which may adversely modulate synaptic and membrane functions; the cerebral energy metabolism and particularly the hexokinase reaction, by Al replacement of the Mg-ion in the Mg-ATP complex, so that phosphorylation of glucose to G6P is blocked; the interaction of Al with calmodulin by displacement of the Ca-ion and subsequent formation of a stable Al-calmodulin complex with a cytotoxic effect due to the increase in the intracellular calcium concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The physiopathologic bases of the neurotoxicity of phosphorus chelating agents containing soluble aluminum salts in patients with renal insufficiency]. 266 59

The effect of parathyroidectomy and/or vitamin D on the development of arterial and myocardial lesions was studied in rats with moderate uraemia. The activities of hexokinase and adenylate kinase in the aorta, myocardium and skeletal muscle were measured and the incidence of aortic calcification and muscle cell necrosis determined. There was a decreased hexokinase activity in the aorta, myocardium and skeletal muscle from uraemic rats. Adenylate kinase showed an increased activity in the same tissues. Parathyroidectomy as well as I-alpha-hydroxycholecalciferol in a dose of 3 ng/100 g b.w. normalized these activities to a great extent. This effect did not occur when 10 ng/100 g b.w. was given. Parathyroidectomy in combination with a low dose of I-alpha-OH-D3 reduced the incidence of myocardial necrosis. Aortic calcifications were found in uraemic animals given 10 ng/100 g b.w. of I-alpha-hydroxycholecalciferol. In this group increased activity of adenylate kinase was found in calcified aortae but not in non-calcified aortae. The study shows that uraemia causes metabolic changes in the aorta, myocardium, and skeletal muscle which may partly be prevented by parathyroidectomy and by low doses of vitamin D. It also indicates some parallelism between these metabolic changes and the development of histologically demonstrable lesions in the aorta.
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PMID:Hexokinase and adenylate kinase activities in aorta, heart muscle and skeletal muscle from uraemic rats. 304 65

Glucose was measured by the ferricyanide, the Beckman glucose oxidase, and the hexokinase procedures in 228 plasma samples taken during standard oral glucose-tolerance tests in 17 normal subjects and in 21 chemical diabetics. The neocuproine method was also used to measure glucose concentration in 156 samples (78 before and 78 after dialysis) collected from six diabetic and uremic patients who were on maintenance hemodialysis. Ferricyanide in all conditions and neocuproine in uremic patients overestimated glucose concentrations over the entire experimental range as compared with either enzymic method. This bias or systematic error of the reducing vs the enzymic procedures, due to nonglucose reducing substances ("saccharoids"), becomes considerably greater when their concentration is increased as in chronic uremia. Also, the inverse relation between glucose concentration and overestimation of glucose by the reducing methods has been detected. With respect to the hexokinase method, a mild but significant underestimate of glucose oxidase readings has been observed for higher glucose concentrations. We find neocuproine to be the most imprecise of these procedures.
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PMID:Four methods for glucose assay compared for various glucose concentrations and under different clinical conditions. 713 20