Substrate specificity at the alkane binding sites of hemoglobin and myoglobin

Wishnia, Arnold

doi:10.1021/bi00840a058

Cited by 27 publications

(8 citation statements)

References 6 publications

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“…Outside the axon these sinks comprise Schwann cell membranes and organelles (Adelman, Moses & Rice, 1977) while the inside of the axon contains mitochondrial membranes and axoplasmic proteins which may also adsorb n-alkane. The affinity of axoplasmic proteins for n-alkanes is unknown but significant binding of n-alkanes to haemoglobin has been observed (Wishnia, 1969). If a simple model is assumed in which the axon and its associated sheath behaves as a homogenous solid cylinder then the radial diffusion time to each cylindrical plane within the structure varies as the square of the total cylinder diameter (Carslaw & Jaeger, 1947;Rud, 1961).…”

Section: Discussionmentioning

confidence: 99%

Nerve impulse blockage in squid axons by n‐alkanes: the effect of axon diameter.

Haydon¹,

Hendry²

1982

The Journal of Physiology

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SUMMARY1. The anaesthetic effects of aqueous solutions of the n-alkanes pentane to nonane on the propagated action potential of squid axons have been investigated for a range of axon diameters.2. By the use of small axons (approx. 200 jtm diameter) to minimize effects due to long diffusion times and alkane depletion it was found that n-pentane and n-hexane caused a rapid reversible inhibition of the impulse, while higher homologues had progressively less effect, n-nonane being apparently inert.3. The rate of action potential decline due to the n-alkanes was found to be strongly dependent on axon diameter. For n-hexane, n-heptane and n-octane the rate of decline was inversely proportional to the square of the axon diameter.4. The mechanisms which may underly the increased sensitivity of small axons to impulse blockade by n-alkanes are discussed. A quantitative comparison is made between the effects of n-hexane, n-heptane and n-octane on the action potential. It is argued that this supports the idea of a real decline in anaesthetic potency on ascending the homologous series, rather than an effect due to long diffusion times and solution depletion.

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Section: Discussionmentioning

confidence: 99%

Nerve impulse blockage in squid axons by n‐alkanes: the effect of axon diameter.

Haydon¹,

Hendry²

1982

The Journal of Physiology

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“…However, its low water and lipid solubilities (7) and minimal solvent chemical shift variation (8) make it an unlikely candidate for differential studies of lung gas and tissue-dissolved phases and may make it uncompetitive with 'H MRI in other tissues. ' "Xe, on the other hand, is 10 times more soluble in water and over 100 times more soluble in apolar phases ( g -l l ) , binds strongly to proteins (12), can be polarized much more rapidly, and shows very large chemical shift differences between gas and solution environments (131. ' Imaging of inhaled laser-polarized "' Xe may have significant advantages for evaluation of physiological function.…”

Section: Introductionmentioning

confidence: 99%

In vivo MR imaging and spectroscopy using hyperpolarized ¹²⁹Xe

Wagshul¹,

Button²,

Li³

et al. 1996

Magnetic Resonance in Med

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141

107

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Hyperpolarized 129Xe has been used to obtain gas phase images of mouse lung in vivo, showing distinct ventilation variation as a function of the breathing cycle. Spectra of 129Xe in the thorax show complex structure in both the gas phase (-4 to 3 ppm) and tissue-dissolved (190-205 ppm) regions. The alveolar gas peak shows correlated intensity and frequency oscillations, both attributable to changes in lung volume during breathing. The two major dissolved peaks near 195-200 ppm are attributed to lung parenchyma and to blood; they reach maximum intensity in 5-10 s and decay with an apparent T1 of 30 s. Another peak at 190 ppm takes 20-30 s to reach maximum; this must represent other well-vascularized tissue (e.g., heart and other muscles) in the thorax. The maximum integrated area of the tissue components reaches 30-80% of the maximum alveolar gas area, indicating that imaging at tissue frequencies can be achieved.

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“…We did not take into account binding to blood proteins in our model, despite evidence that n-alkane-like compounds partition into red blood cells (RBCs) and bind reversibly to hydrophobic sites on hemogloblin and myoglobin (Wishnia, 1969). The extent of binding appears greater in rats than in humans.…”

Section: Discussionmentioning

confidence: 99%

Improved Predictive Model forn-Decane Kinetics Across Species, as a Component of Hydrocarbon Mixtures

Merrill

Gearhart

Sterner

et al. 2008

Inhalation Toxicology

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n-Decane is considered a major component of various fuels and industrial solvents. These hydrocarbon products are complex mixtures of hundreds of components, including straight-chain alkanes, branched chain alkanes, cycloalkanes, diaromatics, and naphthalenes. Human exposures to the jet fuel, JP-8, or to industrial solvents in vapor, aerosol, and liquid forms all have the potential to produce health effects, including immune suppression and/or neurological deficits. A physiologically based pharmacokinetic (PBPK) model has previously been developed for ndecane, in which partition coefficients (PC), fitted to 4-h exposure kinetic data, were used in preference to measured values. The greatest discrepancy between fitted and measured values was for fat, where PC values were changed from 250-328 (measured) to 25 (fitted). Such a large change in a critical parameter, without any physiological basis, greatly impedes the model's extrapolative abilities, as well as its applicability for assessing the interactions of n-decane or similar alkanes with other compounds in a mixture model. Due to these limitations, the model was revised. Our approach emphasized the use of experimentally determined PCs because many tissues had not approached steady-state concentrations by the end of the 4-h exposures. Diffusion limitation was used to describe n-decane kinetics for the brain, perirenal fat, skin, and liver. Flow limitation was used to describe the remaining rapidly and slowly perfused tissues. As expected from the high lipophilicity of this semivolatile compound (log K ow = 5.25), sensitivity analyses showed that parameters describing fat uptake were next to blood:air partitioning and pulmonary ventilation as critical in determining overall systemic circulation and uptake in other tissues. In our revised model, partitioning into fat took multiple days to reach steady state, which differed considerably from the previous model that assumed steady-state conditions in fat at 4 h post dosing with 1200 ppm. Due to these improvements, and particularly the reconciliation between measured and fitted partition coefficients, especially fat, we have greater confidence in using the proposed model for dose, species, and route of exposure extrapolations and as a harmonized model approach for other hydrocarbon components of mixtures.Hydrocarbon mixtures are complex and include straightchain alkanes, branched and cyloalkanes, diaromatics, and naphthalenes. JP-8 jet fuel, for example, generally contains about 18% aromatic hydrocarbons, and the rest is aliphatic hydrocarbons (1996). In order to develop mechanistic tools capable of predicting dose-response from human exposures to jet fuel, it is necessary to provide links between kinetic models and mechanisms of action, together with a framework for additional interaction. Physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) models represent a means of integrating diverse data sets in a mechanism-based analysis. The approach proposed here is to initially develop single-chemical PBPK models...

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Substrate specificity at the alkane binding sites of hemoglobin and myoglobin

Cited by 27 publications

References 6 publications

Nerve impulse blockage in squid axons by n‐alkanes: the effect of axon diameter.

Nerve impulse blockage in squid axons by n‐alkanes: the effect of axon diameter.

In vivo MR imaging and spectroscopy using hyperpolarized ¹²⁹Xe

Improved Predictive Model forn-Decane Kinetics Across Species, as a Component of Hydrocarbon Mixtures

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Substrate specificity at the alkane binding sites of hemoglobin and myoglobin

Cited by 27 publications

References 6 publications

Nerve impulse blockage in squid axons by n‐alkanes: the effect of axon diameter.

Nerve impulse blockage in squid axons by n‐alkanes: the effect of axon diameter.

In vivo MR imaging and spectroscopy using hyperpolarized 129Xe

Improved Predictive Model forn-Decane Kinetics Across Species, as a Component of Hydrocarbon Mixtures

Contact Info

Product

Resources

About

In vivo MR imaging and spectroscopy using hyperpolarized ¹²⁹Xe