Energy Metabolism in Human Platelets:Interrelationship Between Glycolysis and Oxidative Metabolism

Doery, James C.G.; Hirsh, Jack; Cooper, I.

doi:10.1182/blood.v36.2.159.159

Cited by 74 publications

(42 citation statements)

References 24 publications

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“…1 nmol/10 10 platelets/h) could be due to the fact that the rate of free fatty acid oxidation is concentration-dependent (Steiner & Kuramoto, 1971). The concentration of free fatty acids was very low in our medium (about 15 mM), compared to that in all of the other studies, where the concentration of free fatty acids was at least 70 mM (Rock et al, 1991;Spector et al, 1970;Doery et al, 1970;Cesar et al, 1987). The second possible explanation for the low utilization rate is the exhaustion of carnitine which is essential for the oxidation of long-chain free fatty acids.…”

Section: Carbohydrate Metabolismcontrasting

confidence: 56%

“…The rates of free fatty acid oxidation vary from 7 . 2 to 110 nmol (palmitate, oleate or linoleate) per 10 10 platelets per hour depending on the medium composition, the ratio of free fatty acid to albumin, temperature, length of the incubations, chain length of the free fatty acids added to the media and the type of labelled isotope employed (Cohen & Wittels, 1970;Spector et al, 1970;Doery et al, 1970;Donabedian & Nemerson, 1971;Cesar et al, 1987). Palmitate has been reported to be a significant oxidative fuel during platelet storage, accounting for at least 27% of oxygen consumption and 20% of total ATP turnover in plasma (Cesar et al, 1987).…”

Section: Carbohydrate Metabolismmentioning

confidence: 99%

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Types and sources of fuels for platelets in a medium containing minimal added fuels and a low carryover plasma

1997

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Summary. The storage of platelets in synthetic media can result in plasma savings and reduced transfusion reactions. Accordingly, a wide range of storage formulations have been developed with the aim of replacing at least a proportion of the plasma in the storage medium. However, the concentrations and types of fuels in the carryover plasma, and the utilization of these fuels by platelets in storage, has not been investigated. We have developed a system which can measure total ATP turnover, and the contribution to total ATP turnover by the oxidation of various fuels and by lactate production, in a bag of partially purified platelets in a buffered saline with minimal carryover citrate phosphate double dextrose (CP2D) plasma.Carryover plasma was about 1% and the final platelet suspension contained, on average, 0 . 62 mM glucose, 9 . 6 mg/l free fatty acids, 32 mg/l triglycerides and 0 . 23 mM total amino acids. The oxidation of carbohydrate (glucose, glycogen and lactate) accounted for 60% of total ATP turnover. The platelets also produced lactate (<6% of total ATP turnover) and consumed free fatty acids and amino acids/proteins (15 . 2% of total ATP turnover). Therefore we have identified the fuels that account for about 80% of oxygen consumption and ATP turnover by platelets in a medium with low carryover plasma. The implications of these data for storage strategies are discussed.Keywords: platelet storage, fuel, plasma, oxygen.In the past 10 years, significant progress has been made in the development of practical and effective synthetic media for the blood bank storage of platelets, with the promise of considerable saving of plasma, fewer transfusion reactions and longer storage (Moroff & Holme, 1991;Kickler, 1991;Rock et al, 1985Rock et al, , 1991Adams & Rock, 1988;Murphy et al, 1995). A wide range of storage formulations have been developed, most of which are effective in replacing a proportion of the plasma, and good storage results have been reported with platelet additive solutions containing acetate Guppy et al, 1990;Whisson et al, 1993) and glucose (Holme et al, 1987b). However, there are still only minimal data on the potential contribution of the plasma to the fuels available in a minimal plasma medium, and on platelet utilization of these plasma-derived fuels. There are studies that shed some light on these questions, but most of the media used in these studies contain high contaminations (7-40%) of carryover plasma, and high-glucose-anticoagulant (resulting in glucose concentrations of 4-12 mM) which confound the results (e.g. et al, 1987b;Bertolini et al, 1992). The exceptions are the studies by Shimizu et al (1993) and Whisson et al (1993), in which the carryover plasma is about 1%. In addition, even when most of the plasma is removed, all of the studies above concentrate only on the effect of selected fuels on the viability and function of platelets, whereas other candidate fuels are ignored. Finally, few studies have measured total oxygen consumption and thus total ATP turnover, so it is impossi...

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Section: Carbohydrate Metabolismcontrasting

confidence: 56%

Section: Carbohydrate Metabolismmentioning

confidence: 99%

Types and sources of fuels for platelets in a medium containing minimal added fuels and a low carryover plasma

1997

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“…10"' platelets-' . h-' (Guppy et al, 1990;Doery et al, 1970), but there is a plethora of data in the literature on platelet storage for transfusion that supports the notion that only 1-2% of glucose utilized is oxidized by platelets (Guppy et al, 1990;Murphy, 1995;Farrugia, 1994). Acetate is oxidized very rapidly by purified platelets (1.62 pmol .…”

Section: Discussionmentioning

confidence: 97%

“…10'" platelets-. h-l (Doery et al, 1970) and the rates of oxidation of different fatty acids (supplied at 70 pM) can be summarized as linoleic > oleic = stearic > palmitic (Spector et al, 1970). However, fatty acid utilization is very sensitive to the fatty acid/albumin ratio, and the free concentrations of different fatty acids will differ at the same fatty acid/albumin ratio.…”

Section: Discussionmentioning

confidence: 99%

Fuel Choices by Human Platelets in Human Plasma

Guppy

Abas

Neylon

et al. 1997

European Journal of Biochemistry

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Despite the fact that homogeneous preparations of isolated cells are now being used very effectively to study a range of important biochemical questions, it is still not known what combination of fuels and energy-producing pathways is used by cells when offered the complex mixture characteristic of plasma or extracellular fluid. We have developed an in vitro system whereby highly purified and functional human platelets are incubated in human plasma that has been minimally modified from its native state. The concentration of platelets and fuels, and the complexity of fuels in the incubation are similar to those in vivo. The preparation thus represents a reasonable approximation of the physiological condition, considering the complex nature of the system being studied. Measurements carried out simultaneously during the incubation are rates of oxygen consumption, lactate production and fuel oxidation. The data allow the calculation of total ATP turnover, and contributions to this turnover by lactate production and the oxidation of individual fuels. Lactate production accounts for 24% of the ATP turnover. The oxidation of glucose and 3-hydroxybutyrate each account for under S%, palmitate for 21 %, oleate for 7% and acetate for 9%, leaving 32% of the ATP turnover as yet unaccounted for. The results confirm some previous measurements in the literature, but show that data collected under non-physiological experimental conditions can be misleading.Keywords: platelet; oxygen consumption ; plasma; glycolysis ; oxidation.The preparations used for the study of cellular metabolism have progressed over the last 40 years from tissue homogenates and slices to homogeneous preparations of isolated cells. The latter systems are now being used very effectively to study a range of important biochemical questions. However, there is still a question that has never really been adequately addressed, which could have important implications for the relevance of these preparations, and which is fundamental to our understanding of cell biology. This question concerns the combination of fuels and energy-producing pathways used by a cell when it is offered the complex mixture characteristic of plasma or extracellular fluid.Where energy budgets have been presented previously, it is often the case that total ATP turnover has been underestimated due to the omission of any measurement of oxygen consumption. This approach results in overestimates of the contributions of particular fuels and pathways to total ATP turnover as the 'total ATP turnover' figure is too low. For example Petch and Butler (1994) and Neermann and Wagner (1996) conclude that the various pathways of glucose and glutamine utilization account for 100% of ATP turnover in various cell lines in the presence of glucose, glutamine and fetal calf serum. Oxygen consumption was not measured and would almost certainly demonstrate the oxidation of other fuels. Similarly it is now obvious that aerobic glycolysis contributes significantly (20 -50%) to ATP production under aerobic conditions...

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“…Because 2-DOG inhibits uptake of glucose, it not only acts to prevent metabolism via glycolysis, it also inhibits the utilization of glucose in other cell pathways as well. [25][26][27][28][29][30][31] Considering this, it is interesting to note the effect of 2-DOG in this study on the extent of PLT aggregation and clumping. This observation is in agreement with previous findings by other groups.…”

Section: Discussionmentioning

confidence: 99%

Platelet glycolytic flux increases stimulated by ultraviolet‐induced stress is not the direct cause of platelet morphology and activation changes: possible implications for the role of glucose in platelet storage

Li¹,

Goodrich²,

Hansen³

et al. 2005

Transfusion

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Energy Metabolism in Human Platelets:Interrelationship Between Glycolysis and Oxidative Metabolism

Cited by 74 publications

References 24 publications

Types and sources of fuels for platelets in a medium containing minimal added fuels and a low carryover plasma

Types and sources of fuels for platelets in a medium containing minimal added fuels and a low carryover plasma

Fuel Choices by Human Platelets in Human Plasma

Platelet glycolytic flux increases stimulated by ultraviolet‐induced stress is not the direct cause of platelet morphology and activation changes: possible implications for the role of glucose in platelet storage

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