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)

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

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