Skip to main content
SpringerLink
Log in

Albumin-Heme Oxygen Carriers

  • Chapter
  • First Online:
Hemoglobin-Based Oxygen Carriers as Red Cell Substitutes and Oxygen Therapeutics

Abstract

Human serum albumin (HSA) is the most prominent plasma protein in the circulatory system and has a remarkable capability to bind a broad range of hydrophobic molecules. Protoheme IX released from hemoglobin (Hb) is also captured by HSA with a high binding constant. This strong affinity of HSA for heme has stimulated efforts to develop albumin as an artificial hemoprotein which is capable of mimicking the O2 transport of Hb. In this chapter, we report on our representative results of albumin-heme O2 carriers; HSA incorporating synthetic heme, its poly(ethylene glycol) conjugate, and recombinant HSA mutant complexing protoheme IX. These protein hybrids might be of great medical importance not only for RBC alternatives, but also for O2-providing therapeutic reagents.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Adams PA, Berman MC (1980) Kinetics and mechanism of the interaction between human serum albumin and monomeric haemin. Biochem J 191:95–102

    Google Scholar 

  • Antonini E, Brunori M (1971) Hemoglobin and myoglobin in their reactions with ligands. North-Holland Pub, Amsterdam, p 18

    Google Scholar 

  • Bettati S, Mozzarelli A (2011) Chemistry and biochemistry of oxygen therapeutics: from transfusion to artificial blood. John Wiley and Sons, West Sussex

    Google Scholar 

  • Curry S, Madelkow H, Brick P, Franks N (1998) Crystal structure of human serum albumin complexed with fatty acid reveals an asymmetric distribution of binding sites. Nat Struct Biol 5:827–835

    Article  Google Scholar 

  • Curry S, Brick P, Franks N (1999) Fatty acid binding to human serum albumin: new insights from crystallographic studies. Biochim Biophys Acta 1441:131–140

    Article  Google Scholar 

  • Ghuman J, Zunszain PA, Petotpas I, Bhattacharya AA, Otagiri M, Curry S (2005) Structural basis of the drug-binding specificity of human serum albumin. J Mol Biol 353:38–52

    Article  Google Scholar 

  • Gibson QH (1970) The reaction of oxygen with hemoglobin and the kinetic basis of the effect of salt on binding of oxygen. J Biol Chem 245:3285–3288

    Google Scholar 

  • Hess JR, MacDonald VW, Brinkley WW (1993) Systemic and pulmonary hypertension after resuscitation with cell-free hemoglobin. J Appl Physiol 74:1769–1778

    Google Scholar 

  • Hess JR (2006) An update on solutions of red cell storage. Vox Sangunis 91:13–19

    Article  Google Scholar 

  • Huang Y, Komatsu T, Wang RM, Nakagawa A, Tsuchida E (2006a) Poly(ethylene glycol)-conjugated human serum albumin including iron porphyrins: surface modification improves the O2-transporting ability. Bioconjug Chem 17:393–398

    Article  Google Scholar 

  • Huang Y, Komatsu T, Yamamoto H, Horinouchi H, Kobayashi K, Tsuchida E (2006b) PEGylated albumin-heme as an oxygen-carrying plasma expander: exchange transfusion into acute anemia rat model. Biomaterials 27:4477–4483

    Article  Google Scholar 

  • Imai K, Morimoto H, Kotani M, Watari H, Hirata W, Kuroda M (1970) Studies on the function of abnormal hemoglobins I. An improved method for automatic measurement of the oxygen equilibrium curve of hemoglobin. Biochim Biphys Acta 200:189–197

    Article  Google Scholar 

  • Kluger R (2010) Red cell substitutes from hemoglobin—do we start all over again? Curr Opin Chem Biol 14:538–543

    Article  Google Scholar 

  • Kobayashi K (2006) Summary of recombinant human serum albumin development. Biologicals 34:55–59

    Article  Google Scholar 

  • Komatsu T, Hamamatsu K, Wu J, Tsuchida E (1999) Physicochemical properties and O2-coordination structure of human serum albumin incorporating tetrakis(o-pivalamido) phenylporphinatoiron(II) derivatives. Bioconjugate Chem 10:82–86

    Article  Google Scholar 

  • Komatsu T, Okada T, Moritake M, Tsuchida E (2001) O2-binding properties of double-sided porphinatoiron(II)s with polar substituents and their human serum albumin hybrids. Bull Chem Soc Jpn 74:1695–1702

    Article  Google Scholar 

  • Komatsu T, Matsukawa Y, Tsuchida E (2002) Effect of heme structure on O2-binding properties of human serum albumin-heme hybrids: intramolecular histidine coordination provides a stable O2-adduct complex. Bioconjug Chem 13:397–402

    Article  Google Scholar 

  • Komatsu T, Ohmichi N, Zunszain PA, Curry S, Tsuchida E (2004) Dioxygenation of human serum albumin having a prosthetic heme group in a tailor-made heme pocket. J Am Chem Soc 126:14304–14305

    Article  Google Scholar 

  • Komatsu T, Ohmichi N, Nakagawa A, Zunszain PA, Curry S, Tsuchida E (2005) O2 and CO binding properties of artificial hemoproteins formed by complexing iron protoporphyrin IX with human serum albumin mutants. J Am Chem Soc 127:15933–15942

    Article  Google Scholar 

  • Komatsu T, Nakagawa A, Zunszain PA, Curry S, Tsuchida E (2007) Genetic engineering of the heme pocket in human serum albumin: modulation of O2 binding of iron protoporphyrin IX by variation of distal amino acids. J Am Chem Soc 129:11286–11295

    Article  Google Scholar 

  • Komatsu T, Nakagawa A, Curry S, Tsuchida E, Murata K, Nakamura N, Ohno H (2009) The role of an amino acid triad at the entrance of the heme pocket in human serum albumin for O2 and CO binding to iron protoporphyrin IX. Org Biomol Chem 7:3836–3841

    Article  Google Scholar 

  • Kragh-Hansen U (1981) Molecular aspects of ligand binding to serum albumin. Pharmacol Rev 33:17–53

    Google Scholar 

  • Kragh-Hansen U (1990) Structure and ligand-binding properties of human serum-albumin. Danish Med Bull 37:57–84

    Google Scholar 

  • Monzani E, Bonafè B, Fallarini A, Redaelli C, Casella L, Minchiotti L, Galliano M (2001) Enzymatic properties of human serum albumin. Biochim Biophys Acta 1547:302–312

    Article  Google Scholar 

  • Nakagawa A, Komatsu T, Iizuka M, Tsuchida E (2006) Human serum albumin hybrid incorporating tailed porphyrinatoiron(II) in the α, α, α, β-conformer as an O2-binding site. Bioconjug Chem 17:146–151

    Article  Google Scholar 

  • Nakagawa A, Komatsu T, Iizuka M, Tsuchida E (2008) O2 binding to human serum albumin incorporating iron porphyrin with a covalently linked methyl-l-histidine isomer. Bioconjug Chem 19:581–584

    Article  Google Scholar 

  • Natanson C, Kern SJ, Lurie P, Banks SM, Wolfe SM (2008) Cell-free hemoglobin-based blood substitutes and risk of myocardial infarction and death. J Am Med Assoc 299:2304–2312

    Article  Google Scholar 

  • Olson JS, Andersen ME, Gibson QH (1971) The dissociation of the first oxygen molecule from some mammalian oxyhemoglobins. J Biol Chem 246:5919–5923

    Google Scholar 

  • Otani T, Oki K, Akino M, Tamura S, Naito Y, Homma C, Ikeda H, Sumita S (2012) Effect of helicopter transport on red blood cell components. Blood Transfus 10:78–86

    Google Scholar 

  • Petitpas I, Petersen CE, Ha CE, Bhattacharya AA, Zunszain PA, Ghuman J, Bhagavan NV, Curry S (2003) Structural basis of albumin-thyroxine interactions and familial dysalbuminemic hyperthyroxinemia. Proc Natl Acad Sci USA 100:6440–6445

    Article  Google Scholar 

  • Peters T (2006) All about albumin: biochemistry, genetics and medical applications. Academic Press, San Diego

    Google Scholar 

  • Phillips SEV, Schoenborn BP (1981) Neuteon diffraction reveals oxygen-histidine hydrogen bond in oxymyoglobin. Nature 292:81–82

    Article  Google Scholar 

  • Riess JG (2001) Oxygen carriers (“blood substitutes”)- raison d’Etre, chemistry and some physiology. Chem Rev 101:2797–2919

    Article  Google Scholar 

  • Rohlfs R, Mathews AJ, Carver TE, Olson JS, Springer BA, Egeberg KD, Sliger SG (1990) The effects of amino acid substitution at position E7 (residue 64) on the kinetics of ligand binding to serum whale myoglobin. J Biol Chem 265:3168–3176

    Google Scholar 

  • Shaanan B (1983) Structure of human oxyhemoglobin at 2.1 Å resolution. J Mol Biol 171:31–59

    Article  Google Scholar 

  • Sloan EP, Koenigsberg M, Gens D, Cipolle M, Runge J, Mallory MN, Rodman G Jr (1999) Diaspirin cross-linked hemoglobin (DCLHb) in the treatment of severe traumatic hemorrhagic shock: a randomized controlled efficacy trial. J Am Med Assoc 282:1857–1864

    Article  Google Scholar 

  • Squires JE (2002) Artificial blood. Science 295:1002–1005

    Article  Google Scholar 

  • Sugawara Y, Shikama K (1980) Autooxidation of native oxymyoglobin. Eur J Biochem 110:241–246

    Article  Google Scholar 

  • Tsuchida E, Komatsu T, Kumamoto S, Ando K, Nishide H (1995) Synthesis and O2-binding properties of tetraphenylporphyrinatoiron(II) derivatives bearing a proximal imidazole covalently bound at the β-pyrrolic position. J Chem Soc Perkin Trans 2:747–753

    Article  Google Scholar 

  • Tsuchida E, Komatsu T, Mastukawa Y, Hamamatsu K, Wu J (1999) Human serum albumin incorporating tetrakis(o-pivalamido)phenylporphinatoiron(II) derivative as a totally synthetic O2-carrying hemoprotein. Bioconjug Chem 10:797–802

    Article  Google Scholar 

  • Tsuchida E, Komatsu T, Matsukawa Y, Nakagawa Y, Sakai H, Kobayashi K, Suematsu M (2003) Human serum albumin incorporating synthetic heme: red blood cell substitute without hypertension by nitric oxide scavenging. J Biomed Mater Res 64A:257–261

    Article  Google Scholar 

  • Veranese FM, Harris JM (2002) Introduction and overview of peptide and protein PEGylation. Adv Drug Delivery Rev 54:453–456

    Article  Google Scholar 

  • Wardell M, Wang Z, Ho JX, Robert J, Ruker F, Rubel J, Carter DC (2002) The atomic structure of human serum methemalbumin at 1.9 Å. Biochem Biophys Res Commun 291:813–819

    Article  Google Scholar 

  • Winslow RM (2006) Blood substitutes. Elsevier, London

    Google Scholar 

  • Zunszain PA, Ghuman J, Komatsu T, Tsuchida E, Curry S (2003) Crystal structural analysis of human serum albumin complexed with hemin and fatty acid. BMC Struct Biol 3:6

    Article  Google Scholar 

  • Zunszain PA, Ghuman J, McDonagh AF, Curry S (2008) Crystallographic analysis of human serum albumin complexed with 4Z,15E-birirubin-IXα. J Mol Biol 381:394–406

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported by a Grant-in-Aid for Scientific Research on Innovative Area “Coordination Programming” (Area 2107, No. 21108013) from MEXT Japan. The author thanks to Prof. Eishun Tsuchida (Waseda University), Prof. Dr. Stephen Curry (Imperial College London), Prof. Koichi Kobayashi (Keio University), Prof. Hirohisa Horinouchi (Keio University), Prof. Masaki Otagiri (Kumamoto University), and Nipro Corp. for their continuous supports and valuable comments on the artificial blood research.

Author information

Authors and Affiliations

  1. Department of Applied Chemistry, Faculty of Science and Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo, 112-8551, Japan

    Teruyuki Komatsu

Authors
  1. Teruyuki Komatsu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Teruyuki Komatsu .

Editor information

Editors and Affiliations

  1. Brown University, Barrington, Rhode Island, USA

    Hae Won Kim

  2. Brown University, Barrington, Rhode Island, USA

    A. Gerson Greenburg

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Komatsu, T. (2013). Albumin-Heme Oxygen Carriers. In: Kim, H., Greenburg, A. (eds) Hemoglobin-Based Oxygen Carriers as Red Cell Substitutes and Oxygen Therapeutics. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-40717-8_18

Download citation

Publish with us

Policies and ethics

Search

Navigation