Citrate metabolism by human platelets

Abstract

As part of a study on the utilization of substrates by platelets in defined media the metabolism of citrate was measured, since citrate is a common anticoagulant of nearly all such media, and is also an intermediate of oxidative metabolism. Human platelets transferred from plasma to an artificial medium by gel filtration, were incubated with [14C]citrate at 22 degrees C and labelled carbon dioxide produced was measured during short-term incubations of 2 h. Citrate (1 mM) was oxidized to carbon dioxide at low (0.3 nmol per 10(9) platelets h-1) but significant rates, and the oxidation was decreased by the presence of an alternative substrate (acetate) in the medium. There was, however, no significant conversion of citrate to glycogen. It was calculated that under normal storage conditions of platelet concentrates for transfusion purposes, the amount of citrate used cannot decrease citrate concentrations sufficiently to bring about platelet activation.

Systems analysis of metabolism in platelet concentrates during storage in platelet additive solution

“…The lack of intracellular citrate and malate isotopologues, other than uniformly labeled, however, suggest that little, if any, citrate is metabolized within the mitochondria, but rather metabolized to malate within the cytosol during storage. This is consistent with reduced citrate contribution to CO 2 production in platelets in the presence of acetate (32). Combined with the acetate and citrate measurements reported here, our previous metabolomics data quantitatively define the extracellular metabolic changes of PSL.…”

“…In particular, citrate was more actively metabolized in AP-PCs. Citrate oxidation was allowed in our models to take into account previous reports (32), but was low compared to other oxidative fuels. The models suggest that glutamine and to a lesser degree citrate can contribute to ATP production and may serve as alternative ATP sources, with their efficacy being dependent upon the PLT production method and media composition (e.g.…”

Network reconstruction of platelet metabolism identifies metabolic signature for aspirin resistance

“…iAT-PLT-636 was used to investigate the differences between platelet metabolism in normal (ASA-sensitive, ASA-s) and ASA-resistant (ASA-r) individuals. Time course metabolomic and fluxomic ([14C]-labeled metabolites, see Methods) datasets generated from platelets in human plasma at 37°C 15 25 26 27 28 were incorporated into iAT-PLT-636 as constraints on the metabolic reaction fluxes thereby constraining the feasible solution space of the metabolic network. Two different models were built for ASA-s and ASA-r individuals by varying the thromboxane A 2 (TXA 2 ) secretion flux, whose urinary byproduct is believed to be a clinically measurable indicator of ASA resistance 3 (Methods).…”

Comprehensive metabolomic study of platelets reveals the expression of discrete metabolic phenotypes during storage

“…Thus, pyruvate was presumably not oxidized in the TCA cycle for ATP production through oxidative phosphorylation. Other substrates can feed into the TCA cycle coupling oxidative phosphorylation with ATP production,45‐48 but high secretion of succinate in the first 4 days seems to exclude a normal activity of the TCA cycle (Fig. ).…”