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Research Article Free access | 10.1172/JCI107040

Structural and functional studies on hemoglobin Bethesda (α2β2145 His), a variant associated with compensatory erythrocytosis

H. Franklin Bunn, Thomas B. Bradley, William E. Davis, James W. Drysdale, John F. Burke, William S. Beck, and Myron B. Laver

Thorndike Memorial Laboratory, Harvard Medical Service, Boston City Hospital, Boston, Massachusetts 02118

Department of Medicine, Veterans Administration Hospital, University of California, San Francisco, California 94121

Shriners Burns Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114

Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114

Department of Anesthesia, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114

Find articles by Bunn, H. in: PubMed | Google Scholar

Thorndike Memorial Laboratory, Harvard Medical Service, Boston City Hospital, Boston, Massachusetts 02118

Department of Medicine, Veterans Administration Hospital, University of California, San Francisco, California 94121

Shriners Burns Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114

Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114

Department of Anesthesia, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114

Find articles by Bradley, T. in: PubMed | Google Scholar

Thorndike Memorial Laboratory, Harvard Medical Service, Boston City Hospital, Boston, Massachusetts 02118

Department of Medicine, Veterans Administration Hospital, University of California, San Francisco, California 94121

Shriners Burns Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114

Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114

Department of Anesthesia, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114

Find articles by Davis, W. in: PubMed | Google Scholar

Thorndike Memorial Laboratory, Harvard Medical Service, Boston City Hospital, Boston, Massachusetts 02118

Department of Medicine, Veterans Administration Hospital, University of California, San Francisco, California 94121

Shriners Burns Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114

Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114

Department of Anesthesia, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114

Find articles by Drysdale, J. in: PubMed | Google Scholar

Thorndike Memorial Laboratory, Harvard Medical Service, Boston City Hospital, Boston, Massachusetts 02118

Department of Medicine, Veterans Administration Hospital, University of California, San Francisco, California 94121

Shriners Burns Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114

Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114

Department of Anesthesia, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114

Find articles by Burke, J. in: PubMed | Google Scholar

Thorndike Memorial Laboratory, Harvard Medical Service, Boston City Hospital, Boston, Massachusetts 02118

Department of Medicine, Veterans Administration Hospital, University of California, San Francisco, California 94121

Shriners Burns Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114

Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114

Department of Anesthesia, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114

Find articles by Beck, W. in: PubMed | Google Scholar

Thorndike Memorial Laboratory, Harvard Medical Service, Boston City Hospital, Boston, Massachusetts 02118

Department of Medicine, Veterans Administration Hospital, University of California, San Francisco, California 94121

Shriners Burns Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114

Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114

Department of Anesthesia, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114

Find articles by Laver, M. in: PubMed | Google Scholar

Published September 1, 1972 - More info

Published in Volume 51, Issue 9 on September 1, 1972
J Clin Invest. 1972;51(9):2299–2309. https://doi.org/10.1172/JCI107040.
© 1972 The American Society for Clinical Investigation
Published September 1, 1972 - Version history
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Abstract

Studies have been performed on a 12-yr-old Chinese girl with compensatory erythrocytosis due to the presence of hemoglobin Bethesda comprising about 45% of the red cell hemoglobin. Her parents and three siblings were normal. The oxygen affinity of her blood was markedly increased: under physiological conditions (pH 7.40, 37°C). P50 was 12.8 mm Hg (normal = 26.5 mm Hg). The red cell 2,3-diphosphoglycerate (2.3-DPG) level was normal. The abnormal hemoglobin could not be separated from hemoglobin A by zone electrophoresis at pH 8.6 or isoelectric focusing on polyacrylamide gel. However, after the hemoglobin was split into free α and β chains by treatment with p-hydroxymercuribenzoate (PMB) or 6 M urea, an abnormal β chain was readily demonstrated having a higher isoelectric point (more positive net charge) than normal βA. Structural analysis of the variant β chain demonstrated the substitution of histidine for tyrosine at position 145: hemoglobin Bethesda (α2β2145His). From earlier chemical and crystallographic studies, it has been postulated that this residue is a critical determinant of hemoglobin function. Hemoglobin Bethesda was separated from hemoglobin A by column chromatography. Oxygen equilibria of purified hemoglobin Bethesda revealed an extremely high oxygen affinity (exceeding that of isolated α and β chains), and markedly reduced cooperativity. The Bohr effect of hemoglobin Bethesda was 1/3 that of hemoglobin A. However, hemoglobin Bethesda showed a significant interaction with 2.3-DPG and inositol hexaphosphate.

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