By W. N. Aldridge (eds.)
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Additional resources for A Symposium on Mechanisms of Toxicity
The hexobarbitone, if given alone, produces a hypothermia of 1 to 1·5° in about half an hour, which is completely over within 2 h. Fig. 1 also shows that atropine administered a few minutes before the anti-ChE markedly reduces the hypothermia, although it is unable to prevent it completely. Fig. 1 shows the maximum antidotal effect of atropine obtained following an extremely high dose (50 mgfkg, intraperitoneally). Increasing the dose beyond this level produces no better effect, and may kill the rats.
Indeed, the cyclohexane amino-acid is a better substrate than a number of the other glutamic acid derivatives that have been examined (Table 2). TABLE 2. Activity of ovine brain glutamine synthetase toward various substrates* Substrate Relative L-Glutamic acid o-Glutamic acid a-Methyl-L-glutamic acid Threo-,8-methyl-o-glutamic acid Threo-y-methyl-L-glutamic acid ,8-Glutamic acid cis-L-1-Amino-1 ,3-dicarboxycyclohexane * For hydroxamate synthesis (see Vmax 100 54 67 46 63 46 102 Meister, 1968). Inhibition by methionine sulphoximine It has been known for some time that certain derivatives of methioninefor example, methionine sulphone, methionine sulphoxide, and methionine sulphoximine (Fig.
There is an absolute requirement for ATP and one of these metal ions for irreversible inactivation. For example, 98-100% of the activity is inhibited when the enzyme is incubated at pH 7·2 and 37°Cfor 15 min with 5 x to-aM L-methionine-SR-sulphoximine, 0·01 M ATP, and 0·02 M magnesium chloride (or 0·002 M manganese chloride). No inhibition occurs if either the metal ion or ATP is omitted. A number of attempts have been made to reactivate the methionine sulphoximine-inactivated enzyme, but so far reactivation has not been achieved.
A Symposium on Mechanisms of Toxicity by W. N. Aldridge (eds.)