Title: Metabolic tracing analysis reveals substrate-specific metabolic deficits in platelet storage lesion.
Authors: Sims, Carrie; Salliant, Noelle; Worth, Andrew J; Parry, Robert; Mesaros, Clementina; Blair, Ian A; Snyder, Nathaniel W
Published In Transfusion, (2017 11)
Abstract: Storage of platelets (PLTs) results in a progressive defect termed PLT storage lesion (PSL). The PSL is characterized by poor PLT quality on a variety of assays. Metabolic defects are thought to underlie the PSL; thus this study was designed to quantitatively probe specific metabolic pathways over PLT storage.Relative incorporation of stable isotope-labeled substrates was quantified by isotopologue analysis of key acyl-coenzyme A (CoA) thioester products for fresh, viable (after collection, Days 2-5), and expired PLTs (after Day 5). We examined the incorporation of acetate, glucose, and palmitate into acetyl- and succinyl-CoA via liquid chromatography-tandem mass spectrometry.Storage-related defects in the incorporation of acetyl-CoA derived from acetate and palmitate were observed. Carbon derived from palmitate and acetate in succinyl-CoA was reduced over storage time. Glucose incorporation into succinyl-CoA increased in viable PLTs and then decreased in expired PLTs. Carbon derived from octanoate and pyruvate remained partially able to incorporate into acetyl- and succinyl-CoA in expired PLTs, with high variability in pyruvate incorporation.Isotopologue analysis is useful in probing substrate specific defects in the PSL.
PubMed ID: 28836286
MeSH Terms: Acetates/metabolism; Acyl Coenzyme A/metabolism; Blood Platelets/metabolism*; Blood Preservation/standards*; Carbon Isotopes; Chromatography, Liquid; Glucose/metabolism; Humans; Isotope Labeling; Mass Spectrometry; Metabolic Networks and Pathways*; Palmitates/metabolism