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JW Akkerman, G Rijksen, G Gorter and GE Staal
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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| Copyright © 1984 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
