Bo Sörbo

Inhibition of choline acetyltransferase from bovine caudate nucleus by sulfhydryl reagents and reactivation of the inhibited enzyme

Abstract Partly purified choline acetyltransferase from bovine caudate nucleus was inhibited by a number of alkylating, oxidizing and mercaptide-forming sulfhydryl reagents. Substrates and products of the choline acetyltransferase reaction had no or, in the case of acetyl-coenzyme A, only a slight protective effect against the inhibition given by 5,5-dithiobis(2-nitrobenzoate). Reactivation of the enzyme inhibited by the latter compound or by p -mercuribenzoate was achieved with thioglycolate; more efficiently if the inhibition and reactivation was performed at 0° than at higher temperatures.

A comparison of the distribution of some halide ions in the body

Abstract The distribution of the halide ions F − , Br − , I − and tentatively Cl − , and the pseudo-halide ion SCN − has been studied in mice and rats. Whole body autoradiography, microautoradiography, double tracer autoradiography, and scintillation counting methods have been used. Similarities and dissimilarities in the distribution pattern of the various ions are described and discussed. Although the chemical and physical properties are similar for the elements studied—with some notable exceptions for fluorine—their distribution patterns in the body show pronounced dissimilarities.

Protective effect of thiosulfate and metabolic thiosulfate precursors against toxicity of nitrogen mustard (HN2)

Abstract Pharmacokinetic aspects of the protection by thiosulfate against HN 2 toxicity have been studied in mice. Determinations of blood concentrations of HN 2 following subcutaneous injection of the compound demonstrated a rapid resorption of the latter followed by a slower elimination from the blood stream. The effect of time of pretreatment with thiosulfate on the protective effect was correlated to the time course of the blood concentrations of the compound. The kinetics of the reaction between HN 2 and thiosulfate were studied in vitro at pH 7.4 and 37° and the rate constants for the cyclization of HN 2 to its aziridinium ion and for the reaction between the latter and thiosulfate were determined. Chloride ions (0.15 M) were not found to retard the cyclization of HN 2 to its aziridinium ion under these conditions. The results of the in vivo and in vitro experiments are compatible with the current hypothesis of thiosulfate protection being confined to the extracellular space. Attempts were also made to find new antidotes against HN 2 among compounds, which could give rise to thiosulfate inside the cell. Presumptive thiosulfate precursors were evaluated with respect to their thiosulfate-forming capacity in vivo , their reactivity with the aziridinium ion of HN 2 in vitro and their protective effect against HN 2 in mice. The most efficient thiosulfate precursors were alaninethiosulfonate, mercaptopyruvate, propanedithiosulfonate, thiotaurine, and methanethiosulfonate. Only mercaptopyruvate showed a high reactivity with the HN 2 -aziridinium ion and was also the best protective agent, although inferior to thiosulfate in these respects.

Radioprotective effect of aminoalkyl thioesters.

Certain aminoalkyl thioesters were investigated as radioprotective agents. Aminoethyl thiophosphoric acid (as the sodium salt), with a protective effect comparable to that of cysteamine, was the most effective of the compounds studied. (auth)

Conversion of S35-L-Cysteine to Taurine and Sulfate in the Normal and Irradiated Rat

S/sup 35/-l-cysteine was injected into irradiated and control rats, and the excretion of taurine and sulfate followed for 3 days. The excess taurine excreted in the irradiated animals during the first 24 hrs following radiation had about the same specific activity as that of the controls, but during the following 2 days the taurine from the irradiated animals had a higher specific activity. The total amounts of sulfate excreted were the same in both the irradiated and control groups, but the specific activity of the sulfate from the control group was higher on the second and third days. When S/sup 35/-taurine was injected into irradiated and control rats, the taurine excreted had about the same specific activity in both groups. The results may be explained by an initial release of preformed taurine from muscle tissue, and a secondary release of cysteine from tissue proteins in the irradiated animals. (auth)