Mahmoud Abd El Hafez M. Adam

The kinetics of the pH-induced dissociation of the 3 X 10(6) mol wt hemoglobin from Lumbricus terrestris (the earthworm) have been studied in a light-scattering stopped-flow apparatus. The ligand dependent dissociation data were fit well by a simple sequential model. The data for CO and oxyhemoglobin are consistent with Hb12 leads to 2Hb6 leads to 12Hb. Methemoglobin at pH 7 appears to be hexameric and the dissociation is consistent with the model: Hb6 leads to 6Hb. In a sequential decay scheme for which light-scattering changes are monitored, the relative amounts of rapid and slow phase are determined by the rate constants as well as the molecular weights of intermediate species. Assignment of the hexameric intermediate is supported by an investigation of the sensitivity of the theoretical kinetic curves to the molecular weights of the intermediates. This assignment is further supported by the following: (1) the same model will fit the data for oxy- and CO-hemoglobin at all three temperatures (a 24-29-fold variation in rate constants), (2) evidence from electron microscopy shows hexameric forms, and (3) methemoglobin is apparently stable as a hexamer at pH 7. When CO replaces O2 as the ligand, the dissociation rate increases by a factor of four. The met is about 20 times faster than the initial oxyhemoglobin dissociation rate, but perhaps more relevant for comparing dissociation of the hexamer, the met rate was respectively 100 times and 500 times faster than that for the assumed hexameric forms of CO- and oxy-hemoglobin. The activation energies for the dodecamer to hexamer dissociation and for the dissociation of the hexamer to smaller forms were about 30 kcal/mol for oxy-, CO-, and methemoglobin.

Hb Köln (beta 98 Val leads to Met) was found to precipitate rapidly during mechanical shaking. The rate of precipitation of Hb Köln is 5-6 times faster than that of Hb S. The kinetics of precipitation of the patient's hemolysate, which is a mixture of Hb Köln and Hb A, showed a biphasic curve indicating that Hb Köln precipitates independently from Hb A. The instability of Hb Köln may be attributed to the conformational change in the vicinity of heme. The mechanical shaking may be used as a new method for detection and quantitation of hemoglobin Köln and other unstable hemoglobins.

Fluphenazine caused a small decrease in the noradrenaline (NA) concentrations of the rat brain, possibly by impairing granular amine storage. The drug diminished the rise in brain and heart NA concentrations induced by pargyline, suggesting that it might posses inhibitory properties on neuronal uptake mechanisms and/or NA synthesis. Fluphenazine abolished conditioned avoidance responses in rats, an effect which was maintained after the concomitant administration of pargyline, when NA concentrations remained high. This suggests that the fluphenazine-induced sedation is not mediated via its effect on brain NA content, but is possibly due to the effect of the drug on NA turnover rates in the brain.

Fluphenazine caused a small decrease in the noradrenaline (NA) concentrations of the rat brain, possibly by impairing granular amine storage. The drug diminished the rise in brain and heart NA concentrations induced by pargyline, suggesting that it might posses inhibitory properties on neuronal uptake mechanisms and/or NA synthesis. Fluphenazine abolished conditioned avoidance responses in rats, an effect which was maintained after the concomitant administration of pargyline, when NA concentrations remained high. This suggests that the fluphenazine-induced sedation is not mediated via its effect on brain NA content, but is possibly due to the effect of the drug on NA turnover rates in the brain.

Fluphenazine caused a small decrease in the noradrenaline (NA) concentrations of the rat brain, possibly by impairing granular amine storage. The drug diminished the rise in brain and heart NA concentrations induced by pargyline, suggesting that it might posses inhibitory properties on neuronal uptake mechanisms and/or NA synthesis. Fluphenazine abolished conditioned avoidance responses in rats, an effect which was maintained after the concomitant administration of pargyline, when NA concentrations remained high. This suggests that the fluphenazine-induced sedation is not mediated via its effect on brain NA content, but is possibly due to the effect of the drug on NA turnover rates in the brain.

The molecular diamagnetic susceptibility of mercuric iodide has been measured at room temperature and was found to be 138.6 × 10-6 e.m.u. gm mol for the red tetragonal form. A modified Slater-Angus method gave a satisfactory agreement between the calculated and the experimental results if the bond linking mercury and iodine was assumed to be about 60% covalent. The temperature dependence of the susceptibility of mercuric iodide was also determined. © 1975.