Red Blood Cell Metabolism in Pyruvate Kinase Deficient Patients
Background: 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 mecha...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2021.735543/full |
| _version_ | 1818936650932158464 |
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| author | Micaela K. Roy Francesca Cendali Gabrielle Ooyama Fabia Gamboni Holmes Morton Angelo D’Alessandro |
| author_facet | Micaela K. Roy Francesca Cendali Gabrielle Ooyama Fabia Gamboni Holmes Morton Angelo D’Alessandro |
| author_sort | Micaela K. Roy |
| collection | DOAJ |
| description | Background: 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.Methods: Mass spectrometry-based metabolomics analyses were performed on red blood cells (RBCs) from healthy controls (n=10) and PKD patients (n=5).Results: 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.Conclusion: 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. |
| first_indexed | 2024-12-20T05:39:27Z |
| format | Article |
| id | doaj.art-8f34c2691c5a46328dce557380454aac |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-20T05:39:27Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-8f34c2691c5a46328dce557380454aac2022-12-21T19:51:30ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2021-10-011210.3389/fphys.2021.735543735543Red Blood Cell Metabolism in Pyruvate Kinase Deficient PatientsMicaela K. Roy0Francesca Cendali1Gabrielle Ooyama2Fabia Gamboni3Holmes Morton4Angelo D’Alessandro5Department of Biochemistry and Molecular Genetics, University of Colorado Denver – Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Biochemistry and Molecular Genetics, University of Colorado Denver – Anschutz Medical Campus, Aurora, CO, United StatesCentral Pennsylvania Clinic, A Medical Home for Special Children and Adults, Belleville, PA, United StatesDepartment of Biochemistry and Molecular Genetics, University of Colorado Denver – Anschutz Medical Campus, Aurora, CO, United StatesCentral Pennsylvania Clinic, A Medical Home for Special Children and Adults, Belleville, PA, United StatesDepartment of Biochemistry and Molecular Genetics, University of Colorado Denver – Anschutz Medical Campus, Aurora, CO, United StatesBackground: 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.Methods: Mass spectrometry-based metabolomics analyses were performed on red blood cells (RBCs) from healthy controls (n=10) and PKD patients (n=5).Results: 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.Conclusion: 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.https://www.frontiersin.org/articles/10.3389/fphys.2021.735543/fullred blood cells (erythrocytes)pyruvate kinase deficiencymetabolomicsoxidative stressunderrepresented minoritiesrural America |
| spellingShingle | Micaela K. Roy Francesca Cendali Gabrielle Ooyama Fabia Gamboni Holmes Morton Angelo D’Alessandro Red Blood Cell Metabolism in Pyruvate Kinase Deficient Patients Frontiers in Physiology red blood cells (erythrocytes) pyruvate kinase deficiency metabolomics oxidative stress underrepresented minorities rural America |
| title | Red Blood Cell Metabolism in Pyruvate Kinase Deficient Patients |
| title_full | Red Blood Cell Metabolism in Pyruvate Kinase Deficient Patients |
| title_fullStr | Red Blood Cell Metabolism in Pyruvate Kinase Deficient Patients |
| title_full_unstemmed | Red Blood Cell Metabolism in Pyruvate Kinase Deficient Patients |
| title_short | Red Blood Cell Metabolism in Pyruvate Kinase Deficient Patients |
| title_sort | red blood cell metabolism in pyruvate kinase deficient patients |
| topic | red blood cells (erythrocytes) pyruvate kinase deficiency metabolomics oxidative stress underrepresented minorities rural America |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2021.735543/full |
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