AUTHOR=Roy Micaela K. , Cendali Francesca , Ooyama Gabrielle , Gamboni Fabia , Morton Holmes , D’Alessandro Angelo 

TITLE=Red Blood Cell Metabolism in Pyruvate Kinase Deficient Patients

JOURNAL=Frontiers in Physiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2021.735543

DOI=10.3389/fphys.2021.735543

ISSN=1664-042X

ABSTRACT=<p><bold>Background:</bold> Pyruvate kinase deficiency (PKD) is the most frequent congenital enzymatic defect of glycolysis, and one of the most common causes of hereditary non spherocytic hemolytic anemia. Therapeutic interventions are limited, in part because of the incomplete understanding of the molecular mechanisms that compensate for the metabolic defect.</p><p><bold>Methods:</bold> Mass spectrometry-based metabolomics analyses were performed on red blood cells (RBCs) from healthy controls (<italic>n</italic>=10) and PKD patients (<italic>n</italic>=5).</p><p><bold>Results:</bold> In PKD patients, decreases in late glycolysis were accompanied by accumulation of pentose phosphate pathway (PPP) metabolites, as a function of oxidant stress to purines (increased breakdown and deamination). Markers of oxidant stress included increased levels of sulfur-containing compounds (methionine and taurine), polyamines (spermidine and spermine). Markers of hypoxia such as succinate, sphingosine 1-phosphate (S1P), and hypoxanthine were all elevated in PKD subjects. Membrane lipid oxidation and remodeling was observed in RBCs from PKD patients, as determined by increases in the levels of free (poly-/highly-unsaturated) fatty acids and acyl-carnitines.</p><p><bold>Conclusion:</bold> In conclusion, in the present study, we provide the first overview of RBC metabolism in patients with PKD. Though limited in scope, the study addresses the need for basic science to investigate pathologies targeting underrepresented minorities (Amish population in this study), with the ultimate goal to target treatments to health disparities.</p>