The electron-transfer mechanism of autoxidation for hemoglobin, myoglobin, and their iron(II) cyclidene models

Dickerson, Lyndel D.; Sauer-Masarwa, Alexandra; Herron, Norman; Fendrick, Carol M.; Busch, Daryle H.

doi:10.1021/ja00062a028

Cited by 35 publications

(30 citation statements)

References 5 publications

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“…A time constant of 8 h was determined, compared with 48 h for HbA under identical conditions. These results follow the inverse correlation between the rate of autooxidation and the affinity of the heme for oxygen as reported by Brantley et al (1993) and Dickerson et al (1993). We have used the enzyme system of Hayashi et al (1973) to attempt a reduction of the p chains under 10.1 kPa 0,.…”

Section: Resultssupporting

confidence: 84%

Recombinant [Pheβ63]Hemoglobin Shows Rapid Oxidation of the β Chains and Low‐Affinity, Non‐Cooperative Oxygen Binding to the α Subunits

Kiger¹,

Baudin²,

Desbois³

et al. 1997

European Journal of Biochemistry

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We have engineered αβ2 [Phe63]hemoglobin by changing the highly conserved distal histidine of the β chains to a phenylalanine. The mutant tetramer binds four high‐affinity ligands, such as CO or NO, to the ferrous form, or CN to the oxidized iron; however, it binds only two low‐affinity ligands, oxygen and azide. The absorption spectrum of the ferrous deoxy or ferric forms are not normal, displaying an enhanced absorption of the visible band near 560 nm. Half of the autooxidation process, attributed to the mutated β subunits, is over 1000‐fold faster than for Hb A. The mutant Hb exhibits non‐cooperative binding of two oxygens with an affinity about fivefold lower than those of HbA valency hybrids (αmetβ)2. Functional properties of this mutant Hb resemble those of Hb Saskatoon ([Tyr63]Hb) [Suzuki, T., Hayashi, A., Shimizu, A. & Yamamura, Y. (1966) Biochim. Biophys. Acta 127, 280–2821, Flash‐photolysis experiments also indicate non‐cooperative behaviour: the CO‐recombination kinetics were independent of the fraction dissociated. Furthermore, the amplitude of the CO bimolecular phase was the same for the (αcometβ), valency hybrid or the (αcoβco), form, suggesting mainly geminate CO‐recombination kinetics to the β chains. EPR and Resonance Raman spectra did not show evidence for a hemichrome, normally considered as a six‐coordinated iron with low‐spin character. The EPR and resonance Raman spectra for the mutated β subunits demonstrate the presence of a high‐spin compound in the ferric and deoxy ferrous forms. In particular, the ferrous mutated β subunits are penta‐coordinated. The abnormal absorption spectra are possibly due to an interaction between the porphyrin and the phenyl ring in the distal position rather than to direct binding to the iron.

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Section: Resultssupporting

confidence: 84%

Recombinant [Pheβ63]Hemoglobin Shows Rapid Oxidation of the β Chains and Low‐Affinity, Non‐Cooperative Oxygen Binding to the α Subunits

Kiger¹,

Baudin²,

Desbois³

et al. 1997

European Journal of Biochemistry

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“…Alternatively, deoxygenation of the LtEc allowed it to be stored at 37 C for 7 d without significant oxidation or loss of function. This is not surprising, since O 2 is responsible for the auto-oxidation of hemoglobin (Dickerson et al 1993).…”

Section: Discussionmentioning

confidence: 95%

Prolonging the shelf life ofLumbricus terrestriserythrocruorin for use as a novel blood substitute

Muzzelo

Neely

Shah

et al. 2017

Artificial Cells, Nanomedicine, and Biotechnology

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Limitations associated with the storage of red blood cells have motivated the development of novel blood substitutes that are able to withstand long-term storage at elevated temperatures. The hemoglobin of the earthworm Lumbricus terrestris (LtEc) is an attractive blood substitute candidate, since it is resistant to oxidation and aggregation during storage. Several factors were investigated to optimize the thermal and oxidative stability of LtEc during storage, including pH, antioxidant supplements, and deoxygenation. A strategy for the reduction of fully oxidized LtEc with antioxidants was also developed. Overall, LtEc was shown to have the highest thermal stability in Ringer's Modified Lactate solution with 10 mM HEPES at pH 7.0. Deoxygenation of the LtEc was also shown to significantly reduce oxidation of the ferrous heme iron (e.g., %Feafter 7 d at 37 °C = 75.7%). However, even in cases where oxidation does occur, the addition of 1.8 mM ascorbic acid (AA) was found to reduce 98.3% of the oxidized LtEc (37 μM heme). Most importantly, the oxygen transport properties of LtEc were unaffected by storage at high temperatures or oxidation followed by reduction with AA. These results show that LtEc can be stored at high temperatures (37 °C) without any significant loss of function.

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“…Esta caracterização foi feita por Max Perutz e colaboradores da Universidade de Cambridge, em 1959, através de um emprego pioneiro de raios X na caracterização de proteínas. 97 Trata-se de uma hemoproteína intracelular, isto é, se localiza nas hemácias e possui um arranjo tetraédrico, sendo constituída de quatro cadeias polipeptídicas, duas cadeias a e duas cadeias b unidas por interações fracas, não covalentes, como pontes salinas, ligações de hidrogênio e forças de van der Waals.…”

Section: Hemoglobinasunclassified

“…97 A liberação dos gases transportados é também controlada pelo pH, que consiste em um fenômeno conhecido como efeito Bohr. A ligação do oxigênio na hemoglobina é cooperativa, ou seja, a coordenação do O 2 a um heme facilita a coordenação de outra molécula de O 2 com outro heme do mesmo tetrâmero.…”

Section: Hemoglobinasunclassified

“…A recíproca é verdadeira, ou seja, a saída desta molécula de O 2 de um determinado grupo heme facilita a saída das moléculas de O 2 dos outros hemes. 97 O armazenamento do oxigênio é realizado pela mioglobina que está distribuída nos músculos. A mioglobina é um monômero, isto é, constitui-se de uma única sub-unidade, não apresentando o fenômeno da cooperatividade.…”

Section: Hemoglobinasunclassified

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Hemoglobina extracelular gigante de Glossoscolex paulistus: um extraordinário sistema supramolecular hemoproteico

et al. 2011

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Recebido em 26/1/10; aceito em 1/6/10; publicado na web em 22/9/10 GIANT EXTRACELLULAR HEMOGLOBIN OF Glossoscolex paulistus: AN EXTRAORDINARY SUPRAMOLECULAR HEMOPROTEIN SYSTEM. Giant extracellular hemoglobins are considered the summit of complexity in systems that carry oxygen, constituting an extraordinary model system to the study of hemoproteins. This class includes the hemoglobin of the annelid Glossoscolex paulistus that presents high cooperativity, great oligomeric and redox stabilities and ability of oligomeric reassociation. These properties have motivated evaluations about its utilization as prototype of artificial blood and biosensor. Kinetic studies involving autoxidation and detailed spectroscopic characterizations of its ferrous and ferric species have propitiated information about the structure-activity relationship of this macromolecule. The present review analyzes several biochemical issues, evaluating the state-of-art of this subject.Keywords: hemoglobin; ligand exchange; autoxidation. INTRODUÇÃOA hemoglobina extracelular gigante de Glossoscolex paulistus (HbGp) é uma hemoproteína que constitui um sistema carregador de oxigênio in vivo e, consequentemente, credenciado pela seleção natural, apresentando características extremamente interessantes em termos de evolução como, por exemplo, sua possível adaptação a meios ricos em sulfetos.1 Esta hemeproteína apresenta uma extraordinária massa molecular, em torno de 3,1 MDa, 2 com uma unidade estrutural básica altamente organizada, contendo 144 cadeias que apresentam o grupo heme, além da presença de aproximadamente 36 cadeias que não apresentam este grupamento prostético.Os sistemas hemoglobínicos gigantes extracelulares, também conhecidos por eritrocruorinas, 3 constituem arranjos supramoleculares proteicos tão elaborados do ponto de vista da sua relação estrutura/ atividade, que são considerados, segundo Vinogradov, 4,5 o ápice de complexidade em se tratando de hemoproteínas que ligam oxigênio.Além disso, este grupo de hemoglobinas é conhecido por ligações de oxigênio altamente cooperativas.6-8 Entre elas, destaca-se a hemoglobina de Lumbricus terrestris, que vem sendo amplamente estudada por diversos grupos e que apresenta similaridade macromolecular com a hemoglobina de Glossoscolex paulistus. Cálculos por homologia envolvendo o monômero d de Glossoscolex paulistus constataram uma identidade estrutural de 54% em relação ao monômero d de Lumbricus terrestris.A título de ilustração, é interessante mencionar que a hemoglobina de Lumbricus terrestris vem sendo aplicada em pesquisas sobre sangue artifical, 7,9,10 devido à sua natureza extracelular, grande tamanho e resistência à oxidação. Em relação a este último tópico, vale citar os trabalhos de Dorman e colaboradores 9 e Madura e colaboradores 8 que, por meio de estudos espectroeletroquímicos, têm determinado que a hemoglobina de Lumbricus terrestris exibe potenciais redox altamente positivos (de +112 até +61 mV) quando comparados aos potenciais negativos das hemoglobinas tetraméricas e mioglobinas ...

show abstract

The electron-transfer mechanism of autoxidation for hemoglobin, myoglobin, and their iron(II) cyclidene models

Cited by 35 publications

References 5 publications

Recombinant [Pheβ63]Hemoglobin Shows Rapid Oxidation of the β Chains and Low‐Affinity, Non‐Cooperative Oxygen Binding to the α Subunits

Recombinant [Pheβ63]Hemoglobin Shows Rapid Oxidation of the β Chains and Low‐Affinity, Non‐Cooperative Oxygen Binding to the α Subunits

Prolonging the shelf life ofLumbricus terrestriserythrocruorin for use as a novel blood substitute

Hemoglobina extracelular gigante de Glossoscolex paulistus: um extraordinário sistema supramolecular hemoproteico

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