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Observations were made on the acute toxicities in mice of amphetamine and of the monoamine oxidase inhibitors isocarboxazid, mebanazine, nialamide, pargyline, phenelzine and tranylcypromine, with determination of the LD 50 values. Then, the effect of pretreatment of mice with monoamine oxidase inhibitors, or pretreatment with amphetamine, on the LD 50 of amphetamine was determined. The degree of potentiation of amphetamine toxicity by monoamine oxidase inhibitors varied from one to another, the range being from pargyline, which increased the toxicity of amphetamine about 3-fold, to mebanazine which increased it about 100-fold. There was no correlation between the toxicities of the monoamine oxidase inhibitors in mice and the degree to which they potentiated the toxicity of amphetamine. Amphetamine pretreatment was found to have no effect on its own toxicity, determined subsequently.

A purified preparation of the lactate dehydrogenase ( l -lactate:NAD+ oxidoreductase, EC 1.1.1.27) from Streptococcus cremoris, Strain US3, is shown to have an amino acid composition and physical properties similar to those previously reported for a lactate dehydrogenase from Bacillus subtilis. In the pH range 5.0–7.0 and at pH 8.0 in phosphate buffer, the S. cremoris enzyme is characterized by a mol. wt. of 140 000 and frictional ratio 1.26. In contrast, at pH ≥ 7.8 in triethanolamine HCl buffer, the enzyme undergoes a relatively slow unfolding and dissociation resulting in complete conversion at pH 9.0 to an enzymically inactive form of mol. wt. 70 000 and frictional ratio 1.80. Sedimentation velocity experiments at pH 8.0 in triethanolamine-HCl buffer show that the substrate NADH and the activator Fru-1,6-P2 partially stabilize the 140 000 form of the enzyme. Further examination of the size and shape properties of the enzyme at low total concentrations was made by the method of frontal analysis in Sephadex chromatography. It was found that in phosphate buffer an increase of pH in the range 6.0–8.0 (or the addition of NADH or Fru-1,6-P2 at the fixed pH 7.0) decreased the observed elution volume, while the addition of the inhibitor ATP increased it. These results are correlated with initial velocity studies to conclude that the modifiers, ATP and Fru-1,6-P2, induce conformational changes in the structure of the enzyme, the unfolded form being more active.