PMID- 6689946
OWN - NLM
STAT- MEDLINE
DCOM- 19840214
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 63
IP  - 1
DP  - 1984 Jan
TI  - Platelet functions and energy metabolism in a patient with hexokinase deficiency.
PG  - 147-53
AB  - 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.
FAU - Akkerman, J W
AU  - Akkerman JW
FAU - Rijksen, G
AU  - Rijksen G
FAU - Gorter, G
AU  - Gorter G
FAU - Staal, G E
AU  - Staal GE
LA  - eng
PT  - Case Reports
PT  - Journal Article
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Lactates)
RN  - 33X04XA5AT (Lactic Acid)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - 9005-79-2 (Glycogen)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adenosine Triphosphate/blood
MH  - Adult
MH  - Anemia, Hemolytic, Congenital/*blood
MH  - Anemia, Hemolytic, Congenital Nonspherocytic/*blood/enzymology
MH  - Blood Platelets/enzymology/metabolism/*physiology
MH  - Calcium/metabolism
MH  - *Energy Metabolism
MH  - Female
MH  - Glycogen/blood
MH  - Glycolysis
MH  - Hexokinase/*deficiency
MH  - Humans
MH  - Lactates/biosynthesis
MH  - Lactic Acid
MH  - Platelet Aggregation
EDAT- 1984/01/01 00:00
MHDA- 1984/01/01 00:01
CRDT- 1984/01/01 00:00
PHST- 1984/01/01 00:00 [pubmed]
PHST- 1984/01/01 00:01 [medline]
PHST- 1984/01/01 00:00 [entrez]
AID - S0006-4971(20)84476-0 [pii]
PST - ppublish
SO  - Blood. 1984 Jan;63(1):147-53.