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Cited by 20Adenosine and Purinergic SignalingBiochemical and Molecular ResearchHemoglobin structure and function

CD73 and AMPD3 deficiency enhance metabolic performance via erythrocyte ATP that decreases hemoglobin oxygen affinity

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O’Brien III, William G., Berka, Vladimir, Tsai, Ah-Lim, Zhao, Zhaoyang, Lee, Cheng Chi·2015·Scientific Reports
DOI 10.1038/srep13147PMC PMC4650700
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Abstract

Erythrocytes are the key target in 5′-AMP induced hypometabolism. To understand how regulation of endogenous erythrocyte AMP levels modulates systemic metabolism, we generated mice deficient in both CD73 and AMPD3, the key catabolic enzymes for extracellular and intra-erythrocyte AMP, respectively. Under physiological conditions, these mice displayed enhanced capacity for physical activity accompanied by significantly higher food and oxygen consumption, compared to wild type mice. Erythrocytes from Ampd3−/− mice exhibited higher half-saturation pressure of oxygen (p50) and about 3-fold higher levels of ATP and ADP, while they maintained normal 2,3-bisphosphoglycerate (2,3-BPG), methemoglobin levels and intracellular pH. The affinity of mammalian hemoglobin for oxygen is thought to be regulated primarily by 2,3-BPG levels and pH (the Bohr effect). However, our results show that increased endogenous levels of ATP and ADP, but not AMP, directly increase the p50 value of hemoglobin. Additionally, the rise in erythrocyte p50 directly correlates with an enhanced capability of systemic metabolism.

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  • Since ATP is an allosteric effector that stabilizes O2-unloaded hemoglobin in vertebrates, the loss of AMPD3 results in a reduced O2 affinity of hemoglobin.

    “Since ATP is an allosteric effector that stabilizes O2-unloaded hemoglobin in vertebrates, the loss of AMPD3 results in a reduced O2 affinity of hemoglobin28.”

    From A genomics approach reveals insights into the importance of gene losses for mammalian adaptations (2018) · cites this paper as [28]

    The Results section, “Modulation of hemoglobin’s oxygen saturation by ATP” (page unavailable), reports that AMPD3-deficient erythrocytes have higher ATP and a higher hemoglobin p50, consistent with reduced oxygen affinity. The Discussion (page unavailable) also describes ATP binding to hemoglobin, but our copy does not establish the more specific mechanism that ATP stabilizes oxygen-unloaded hemoglobin across vertebrates. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • AMPD3 encodes an erythrocyte-specific enzyme whose knockout in mice increases the erythrocyte ATP level by threefold.

    “AMPD3 encodes an erythrocyte-specific enzyme whose knockout in mice increases the erythrocyte ATP level by threefold28.”

    From A genomics approach reveals insights into the importance of gene losses for mammalian adaptations (2018) · cites this paper as [28]

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Authors
O’Brien III, W. G., Berka, V., Tsai, A.-L., Zhao, Z., & Lee, C. C.
Affiliations
The University of Texas Health Science Center at Houston (US)
Corresponding author
Lee, Cheng Chi
ORCID
Zhao, Zhaoyang
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2015-08-07
Volume
5
Issue
1
Pages
13147-13147
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/srep13147
PMC
PMC4650700
OpenAlex
W1172574862
Cited by
20
References
0
Citations by year
2026: 1 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 3 · 2016: 1
FWCI
1.41
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
Keywords
CD73, AMPD3, erythrocyte ATP, hemoglobin oxygen affinity, 2,3-diphosphoglycerate, Bohr effect, physical activity, oxygen consumption, dietary intake, systemic metabolism, methemoglobin, intracellular pH
MeSH terms
Adenosine Diphosphate, Adenosine Triphosphate, AMP Deaminase, Animals, Biochemical Phenomena, Erythrocytes, Female, Hemoglobins, Hydrogen-Ion Concentration, Male, Oxygen, 5'-Nucleotidase, 2,3-Diphosphoglycerate, Mice

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