Evidence map›Paper›PMID 26460266›Full record

ArticleBlood cells, molecules & diseases2015

The free heme concentration in healthy human erythrocytes.

Anupam Aich, Melissa Freundlich, Peter G Vekilov

Abstract read
In one paragraph

Article in Blood cells, molecules & diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. A reversible feedback mechanism regulating mitochondrial heme synthesis.bioRxiv : the preprint server for biology · 2025
    Article
  6. Whole blood exchange ameliorates acute hemolytic anemia by reducing inflammation and oxidative stress in rats.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  7. Article
  8. Article
  9. Review
  10. Histidine-rich protein II nanoparticle delivery of heme iron load drives endothelial inflammation in cerebral malaria.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  11. The NLRP3 inflammasome fires up heme-induced inflammation in hemolytic conditions.Translational research : the journal of laboratory and clinical medicine · 2023
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors.

Anupam AichDepartment of Chemical and Biomolecular Engineering, University of Houston, 4800 Calhoun Road, Houston, TX 77204, USA.
Melissa FreundlichDepartment of Chemical and Biomolecular Engineering, University of Houston, 4800 Calhoun Road, Houston, TX 77204, USA; École Nationale Supérieure de Chimie de Paris, 11, rue Pierre et Marie Curie, 75231 PARIS Cedex 05, France.
Peter G VekilovDepartment of Chemical and Biomolecular Engineering, University of Houston, 4800 Calhoun Road, Houston, TX 77204, USA; Department of Chemistry, University of Houston, 4800 Calhoun Road, Houston, TX 77204, USA. Electronic address: vekilov@uh.edu.

Funding

Multiscale Modeling of Sickle Cell Anemia: Methods and ValidationU01HL114476 · NHLBI · BROWN UNIVERSITY · PI DAO, MING, HIGGINS, JOHN MATTHEW · 2013 to 2017
$3.9M
NHLBI NIH HHS U01 HL114476NHLBI NIH HHS U01HL114476
6 · The paper itself

Abstract

Heme, the prosthetic group of hemoglobin, may be released from its host due to an intrinsic instability of hemoglobin and accumulate in the erythrocytes. Free heme is in the form of hematin (Fe(3+) protoporphyrin IX OH) and follows several pathways of biochemical toxicity to tissues, cells, and organelles since it catalyzes the production of reactive oxygen species. To determine concentration of soluble free heme in human erythrocytes, we develop a new method. We lyse the red blood cells and isolate free heme from hemoglobin by dialysis. We use the heme to reconstitute horseradish peroxidase (HRP) from an excess of the apoenzyme and determine the HRP reaction rate from the evolution of the emitted luminescence. We find that in a population of five healthy adults the average free heme concentration in the erythrocytes is 21±2μM, ca. 100× higher than previously determined. Tests suggest that the lower previous value was due to the use of elevated concentrations of NaCl, which drive hematin precipitation and re-association with apoglobin. We show that the found hematin concentration is significantly higher than estimates based on equilibrium release and the known hematin dimerization. The factors that lead to enhanced heme release remain an open question.

Indexed as

Erythrocyte MembraneErythrocytesHealthy VolunteersHemeHemolysisHumansProtein BindingRenal DialysisHemeEnzymatic analysisHematin concentrationHeme releaseHemoglobin instabilityHuman erythrocytesLuminescence

Identifiers

PMID26460266
PMCPMC4860002

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.