Network reconstruction of platelet metabolism identifies metabolic signature for aspirin resistance.

Abstract:

:Recently there has not been a systematic, objective assessment of the metabolic capabilities of the human platelet. A manually curated, functionally tested, and validated biochemical reaction network of platelet metabolism, iAT-PLT-636, was reconstructed using 33 proteomic datasets and 354 literature references. The network contains enzymes mapping to 403 diseases and 231 FDA approved drugs, alluding to an expansive scope of biochemical transformations that may affect or be affected by disease processes in multiple organ systems. The effect of aspirin (ASA) resistance on platelet metabolism was evaluated using constraint-based modeling, which revealed a redirection of glycolytic, fatty acid, and nucleotide metabolism reaction fluxes in order to accommodate eicosanoid synthesis and reactive oxygen species stress. These results were confirmed with independent proteomic data. The construction and availability of iAT-PLT-636 should stimulate further data-driven, systems analysis of platelet metabolism towards the understanding of pathophysiological conditions including, but not strictly limited to, coagulopathies.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Thomas A,Rahmanian S,Bordbar A,Palsson BØ,Jamshidi N

doi

10.1038/srep03925

subject

Has Abstract

pub_date

2014-01-29 00:00:00

pages

3925

issn

2045-2322

pii

srep03925

journal_volume

4

pub_type

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