Influence of globin structure on the state of the heme. I. Human deoxyhemoglobin

Perutz, M. F.; Ladner, Jane E.; Simon, Sanford R.; Ho, Chien

doi:10.1021/bi00707a026

Cited by 307 publications

(245 citation statements)

References 32 publications

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“…The effect of P 6 -inositol on the oxidation and reduction rates of hemoglobin with pyrogallol may be explained by the conformational changes in oxyhemoglobin and methemoglobin by this organic phosphate, as suggested by Perutz et al (1974). Such acceleration of the reaction rates caused by P 6 -inositol has been indicated in the oxido-reductive reactions of hemoglobin with various oxidants and reductants (Tomoda et al 1977b;Tomoda and Yoneyama 1979).…”

Section: Discussionmentioning

confidence: 92%

Metabolism of Pyrogallol to Purpurogallin by Human Erythrocytic Hemoglobin

Miyazaki

Arai

Iwamoto

et al. 2004

Tohoku J. Exp. Med.

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The aim of this study was to investigate the oxidoreductive reactions of human hemoglobin with pyrogallol and the metabolism of pyrogallol by the protein, which contains a protoporphyrin IX like cytochrome P-450. Pyrogallol, having three hydroxy groups at the adjacent positions in the benzene ring, oxidized human oxyhemoglobin to methemoglobin and reduced human methemoglobin to oxyhemoglobin. Since superoxide dismutase and catalase inhibited these reactions extensively, active oxygens such as superoxide and hydrogen peroxide were considered to be involved in the oxido-reductive reaction of human hemoglobin by pyrogallol. It was also found that the metabolism of pyrogallol to purpurogallin occurred quickly in human erythrocytes, i.e., when pyrogallol was added to human erythrocyte suspension, it oxidized intracellular hemoglobin and produced purpurogallin. The metabolism of pyrogallol to purpurogallin was explained by the pyrogallol oxidation with superoxide and hydrogen peroxide produced during the oxidoreductive reactions of human hemoglobin with pyrogallol. The present results show that human erythrocytes can metabolize pyrogallol, suggesting that the cells may be involved in the metabolism of some drugs in the human body.erythrocytes; hemoglobin; pyrogallol; purpurogallin © 2004 Tohoku University Medical Press Though drug metabolism has been shown to be carried out by cytochrome P-450 in the liver (Omura and Sato 1964;Lu et al. 1972), the contribution of erythrocytic hemoglobin, a protoporphyrin IX containing hemoprotein like cytochrome P-450, to drug metabolism is unlikely to attract much attention. Tomoda et al. (1977a) showed that aniline was metabolized to p-aminophenol by human erythrocytes, in the presence of catalytic amounts of methylene blue. Mieyal and Blumer (1976) demonstrated that oxyhemoglobin can hydroxylate aniline to p-ami-

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Section: Discussionmentioning

confidence: 92%

Metabolism of Pyrogallol to Purpurogallin by Human Erythrocytic Hemoglobin

Miyazaki

Arai

Iwamoto

et al. 2004

Tohoku J. Exp. Med.

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“…Recently Perutz et al [2,3] have shown that this negative CD peak indicates the R to T transition in hemoglobin independent of the degree of ligation. For hemoglobins which crystalize in a structure isomorphous with oxyhemoglobin this negative CD peak is not produced even in the absence of heme ligand.…”

Section: Introductionmentioning

confidence: 95%

Ultraviolet circular dichroism of nitrosyl hemoglobin

Salhany

1974

FEBS Letters

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“…Three different spectra were used to fit the data. The spectrum of CO minus deoxyhemoglobin was taken from the data of Olson and Gibson (7); the spectrum characteristic of affinity change, which we shall call the RT difference spectrum, was taken from the N-ethylsuccinamide des-Arg-hemoglobin data of Perutz et al (8); and for small corrections of residual oxygen, a set of data for CO minus oxyhemoglobin was generated in our lab. The need for an oxygen correction arises since the excitation we produce is only 1% of the total sample, and the out-of-phase spectrum is typically forty times smaller.…”

mentioning

confidence: 99%

Rate of quaternary structure change in hemoglobin measured by modulated excitation.

Ferrone¹,

Hopfield²

1976

Proc. Natl. Acad. Sci. U.S.A.

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Using a novel technique of modulated photodissociation of carbon monoxide from hemoglobin, we have obtained the rates for conversion between the two quaternary states, R and T, at 3fold ligation. Our measurements at pH 7 and 220 give rates of 780 + 40 sec1 for going from R to T, and 2500 i 200 secI from T to R. This yields an equilibrium constant of 0.31 + 0.04, which is in good agreement with previous estimates. The degree of agreement between this equilibrium constant and that predicted from the allosteric model provides a new, quantitative test of the allosteric description. A sequential model for the change in structure was found incompatible with the data, even if kinetic subunit inequivalence was assumed. The technique described here is quite general and can be used as long as the system under investigation can be repetitively excited in a regime in which it responds linearly to the excitation. Efficient oxygen transport by hemoglobin depends on alteration of its affinity in the course of ligand binding. A wide range of kinetic and equilibrium data is described successfully by a two-state, or allosteric model (1), which posits that the affinities are chiefly controlled by the quaternary structure of hemoglobin. The parameters of this model are the ligand binding and release rates for each of the two structures (R and T) and a set of rates for conversion between the R and T structures with zero to four ligands bound to the tetramer. The model requires that the binding and release rates be independent of the degree or level of ligation, although the interconversion rates may differ for the various degrees of ligation. Despite their importance to the model, there have been few measurements of any rates of change between conformational states (2-4), and no measurements of rate pairs from which equilibrium constants between the R and T structures might be obtained.We have studied the kinetics of the binding of the last ligand to the 3fold ligated tetramer by means of modulated excitation, and thereby measured the rates of conversion between R and T structures. This method of kinetic study has unique abilities in measuring the time constants of molecular processes that have similar spectral changes and similar time constants. The technique differs from conventional kinetics in that an excitation is repetitively applied and phase-sensitive detection is used. The latter is superior to signal averaging since it permits large signals to be nulled, revealing much weaker relaxation components. With this method, the optical absorption spectrum of the excited species can be obtained simply by scanning a monochromator, so that the separation of different components in the relaxation is assisted by the wealth of information available from static spectra. We have used a mechanically chopped light beam to drive our Hb(CO)4 sample out of equilibrium. A second beam-the analyzing beam-also passes through the sample to a photodetector. The signal from this detector is fed to a lock-in amplifier. The analyzing beam is mo...

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Influence of globin structure on the state of the heme. I. Human deoxyhemoglobin

Cited by 307 publications

References 32 publications

Metabolism of Pyrogallol to Purpurogallin by Human Erythrocytic Hemoglobin

Metabolism of Pyrogallol to Purpurogallin by Human Erythrocytic Hemoglobin

Ultraviolet circular dichroism of nitrosyl hemoglobin

Rate of quaternary structure change in hemoglobin measured by modulated excitation.

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