Citrate metabolism in red blood cells stored in additive solution-3.

作者: Angelo D'Alessandro , Travis Nemkov , Tatsuro Yoshida , Aarash Bordbar , Bernhard O. Palsson

DOI: 10.1111/TRF.13892

关键词:

摘要: BACKGROUND Red blood cells (RBCs) are thought to have a relatively simple metabolic network compared other human cell types. Recent proteomics reports challenge the notion that RBCs mere hemoglobin carriers with limited activity. Expanding our understanding of RBC metabolism has key implications in many biomedical areas, including transfusion medicine. STUDY DESIGN AND METHODS In-gel digestion coupled mass spectrometric analysis approaches were combined state-of-the-art tracing experiments by incubating leukofiltered additive solution-3 for up 42 days under bank conditions, presence 13C1,2,3-glucose, 2,2,4,4-d-citrate, and 13C,15N-glutamine. RESULTS Results indicate pentose phosphate pathway/glycolysis ratio increases during storage solution-3. While majority supernatant glucose is consumed fuel glycolysis, incorporation glucose-derived moieties was observed nucleoside monophosphates. Incubation deuterated citrate indicated uptake contribute explain origin approximately 20% 30% lactate could not be explained oxidation 2,3-diphosphoglycerate consumption alone. 13C,15N-glutamine showed glutaminolysis fuels transamination reactions accumulation millimolar levels 5-oxoproline, while de novo glutathione synthesis significantly active refrigerated storage. CONCLUSION Quantitative revealed mature can metabolize substrates than glucose, such as citrate, an observation relevant medicine (i.e., formulation novel additives), research endeavors where modulation opens potential avenues therapeutic interventions, sickle disease.

参考文章(49)
Travis Nemkov, Angelo D’Alessandro, Kirk C. Hansen, Three-minute method for amino acid analysis by UHPLC and high-resolution quadrupole orbitrap mass spectrometry Amino Acids. ,vol. 47, pp. 2345- 2357 ,(2015) , 10.1007/S00726-015-2019-9
Angelo D'Alessandro, Travis Nemkov, Kirk C. Hansen, Zbigniew M. Szczepiorkowski, Larry J. Dumont, Red blood cell storage in additive solution-7 preserves energy and redox metabolism: a metabolomics approach Transfusion. ,vol. 55, pp. 2955- 2966 ,(2015) , 10.1111/TRF.13253
Nicole Kresge, Robert D. Simoni, Robert L. Hill, Otto Fritz Meyerhof and the Elucidation of the Glycolytic Pathway Journal of Biological Chemistry. ,vol. 280, ,(2005) , 10.1016/S0021-9258(20)76366-0
Richard O. Francis, Jeffrey Jhang, Jeanne E. Hendrickson, James C. Zimring, Eldad A. Hod, Steven L. Spitalnik, Frequency of glucose-6-phosphate dehydrogenase-deficient red blood cell units in a metropolitan transfusion service Transfusion. ,vol. 53, pp. 606- 611 ,(2013) , 10.1111/J.1537-2995.2012.03765.X
P.S. Low, P. Rathinavelu, M.L. Harrison, Regulation of glycolysis via reversible enzyme binding to the membrane protein, band 3. Journal of Biological Chemistry. ,vol. 268, pp. 14627- 14631 ,(1993) , 10.1016/S0021-9258(18)82379-1
Stephney Whillier, Julia E. Raftos, Rosemary L. Sparrow, Philip W. Kuchel, The effects of long-term storage of human red blood cells on the glutathione synthesis rate and steady-state concentration Transfusion. ,vol. 51, pp. 1450- 1459 ,(2011) , 10.1111/J.1537-2995.2010.03026.X
Lello Zolla, Cristiana Mirasole, Gian Maria D’Amici, Tatsuro Yoshida, Larry J. Dumont, Angelo D’Alessandro, Red blood cell storage in SAGM and AS3: a comparison through the membrane two-dimensional electrophoresis proteome. Vox Sanguinis. ,vol. 10, ,(2012) , 10.2450/2012.008S
Angelo D'Alessandro, Anastasios G. Kriebardis, Sara Rinalducci, Marianna H. Antonelou, Kirk C. Hansen, Issidora S. Papassideri, Lello Zolla, An update on red blood cell storage lesions, as gleaned through biochemistry and omics technologies. Transfusion. ,vol. 55, pp. 205- 219 ,(2015) , 10.1111/TRF.12804