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 effect of thrombin-activated platelets and their release products on the intracellular free calcium concentration ([Ca2+]i) of human polymorphonuclear leukocytes (PMNs) was studied by loading PMNs with a fluorescent indicator of calcium, fura-2. [Ca2+]i of PMNs was transiently elevated by thrombin-activated platelets. The supernatant of thrombin-activated platelets also elicited a transient elevation of [Ca2+]i in PMNs. Pretreatment of the supernatant with hexokinase caused a decrease in the transient [Ca2+]i elevation of PMNs, while hexokinase abrogated the [Ca2+]i elevation of PMNs elicited by 80 mumol/l adenosine triphosphate (ATP). Pretreatment of the supernatant with trypsin also decreased the magnitude of the elevation, while trypsin had no effect on the response to ATP. These findings suggest that thrombin-activated platelets induce a transient [Ca2+]i elevation in PMNs by releasing ATP and some trypsin-sensitive factor(s).
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PMID:Transient calcium elevation in polymorphonuclear leukocytes triggered by thrombin-activated platelets. 159 99

We have studied the regeneration of adenosine triphosphate (ATP) in the glycolytic pathway in platelets with a 75% reduction in hexokinase (HK) activity and have investigated aggregation and Ca2+ secretion. HK-deficient platelets had a normal glycolytic flux in the resting state, but responded insufficiently to stimulation with thrombin (5 U/ml). In contrast, glycogen contents and glycogenolysis were normal. When the metabolic adenine nucleotides were labeled with 14C-adenine, the patient's platelets showed a normal adenylate energy charge and a normal level of 14C-ATP. However, the inhibitor of mitochondrial energy generation, CN-, induced a weaker fall in 14C-ATP in the patient's platelets than in the controls. Analysis of secretion markers revealed decreased amounts of granule-bound ATP and secretable Ca2+, whereas granule-bound adenosine diphosphate (ADP), beta-thromboglobulin, N-acetyl-beta-D-glucosaminidase, and beta-glucuronidase were within the normal range. Aggregation and Ca2+ secretion induced by 5 U/ml thrombin were normal and were not changed in the presence of inhibitors of mitochondrial and glycogenolytic energy generation. Aggregation was also normal at 0.1 U/ml thrombin and was independent of these inhibitors, but Ca2+ secretion was greatly impaired when mitochondrial and glycogenolytic ATP resynthesis was abolished. These findings indicate that a severe reduction in HK activity causes insufficient acceleration of the glycolytic flux during stimulation with thrombin. This leads to impaired dense granule secretion in conditions where secretion depends on concurrent ATP resynthesis and glycolysis is rate limiting.
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PMID:Platelet functions and energy metabolism in a patient with hexokinase deficiency. 668 46

Craviten effect on platelets suspended in their own plasma was investigated by two methods of incubation with the drug: the fresh platelets were incubated for 18 h at 4 degrees C with Craviten added to plasma and platelets stored for 18 h at 4 degrees C without Craviten were incubated with Craviten at 37 degrees C for 1 h. For evaluation of the metabolic activity and function of the platelets, the levels of high-energy compounds ATP and ADP, the activity of hexokinase and pyruvate kinase and the amount of adenyl nucleotides released by the platelets after thrombin addition were measured, and the spontaneous aggregation of platelets and c-AMP were determined. The experiments demonstrated that Craviten prevented the fall of ATP level of the stored platelets, raised the activity of hexokinase and pyruvate kinase in the platelets, increased the amount of nucleotides released by the platelets in the release reaction. Craviten inhibited also increased spontaneous aggregation of stored platelets and raised c-AMP level.
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PMID:Craviten effect on the metabolism of stored platelets. 718 49

Interactions between platelets and polymorphonuclear leukocytes (PMN) modulate their functions and play a role in the development of pathogenesis of some disease. Platelets secret various kinds of factors that affect PMN functions. They seemed to have important role in vivo, but little has been elucidated on exact mechanism of action and physiological meaning of each factor in relation to PMN functions. We studied the effects of platelets and released substances from activated platelets on the functions of PMN. Results were as follows. 1) Platelets enhanced bactericidal activities of PMN against E.coli. 2) Platelets had effects on the generation of superoxide anion (O2-) of PMN. Their effects were quite different according to the assay condition of PMN, that is, platelets inhibited O2- generation when PMN were at rest or stimulated slightly and they enhanced O2-generation of PMN that were stimulated with optimal condition. 3) Thrombin-activated platelets and their supernatant elicited a transient elevation of [Ca2] of PMN. The activity of the supernatant decreased by treating with hexokinase that decomposed ATP. Further treatment with trypsin abolished its activity almost completely. Considering with our additional experiments, factors that induced [Ca2+] elevation of PMN were ATP, beta-thromboglobulin and some trypsin-sensitive factor(s). 4) Supernatant of thrombin-activated platelets decreased random migration and chemokinesis of PMN.
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PMID:[Analysis of platelet-derived factors that modulate functions of polymorphonuclear leukocytes]. 802 84

Blood platelets take up glucose through insulin-independent GLUT-3 transporter. It is, however, unclear how diabetes affects further steps of glucose and glucose-derived acetyl-coenzyme A (CoA) metabolism in platelets. There is no evidence to explain whether these changes are linked to the disease-induced disturbances in platelet function. We found that activities of some key enzymes of glucose and acetyl-CoA metabolism in platelets were elevated in diabetes. Activities of hexokinase, pyruvate dehydrogenase and ATP-citrate lyase in diabetic platelets were found to be increased by 53, 56 and 88%, respectively. Accordingly, diabetes brought about 86% increase of platelet acetyl-CoA and activation of malonyl dialdehyde synthesis as well as spontaneous and thrombin-induced platelet aggregation by about 56, 50 and 15%, respectively. Significant correlations have been observed between some parameters of acetyl-CoA metabolism, platelet function and serum fructosamine in diabetic patients but not in healthy individuals. Our findings indicate that increased platelet activity in diabetic subjects may, at least in part, result from chronic hyperglycaemia-induced changes in acetyl-CoA metabolism, yielding an increase in its concentration in platelets.
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PMID:Platelet function and acetyl-coenzyme A metabolism in type 1 diabetes mellitus. 1459 62