E. Albert Zeller

Snake venom action: Are enzymes involved in it?

Enzymes were the first clearly recognized components of snake venoms. When several more were discovered, attempts were made to correlate venom action with enzymic functions. The last few years have seen most successful efforts in the identification, isolation and structural elucidation of highly toxic polypeptides present in snake venoms, in particular of ‘neurotoxins’ and membrane-active toxins. Following this development the polypeptides were called the true toxic components and the enzymes lost their previous central position in venom pharmacology. The time, therefore, has come to re-evaluate the role of enzymes in the complex interaction between snake and prey. While highly active polypeptides indeed dominate the action of hydrophiid venoms, they appear to play a lesser role in crotalid venom action as compared with enzyme components. Enzymes are involved in many levels of venom action, e. g. by serving as spreading factors, of by producing very active agents, such as bradykinin and lysolecithins in tissues of preys or predators. Some toxins, e. g. the membrane-active polypeptides appear to participate in the interaction between membrane phospholipids and venom phospholipases. The classical neurotoxin, β-bungarotoxin, has been recognized as a powerful phospholipase. Several instances are known which indicate that some enzymes potentiate the toxic action of others; the analysis of a single enzyme may, therefore, not fully reveal its biofunction. For 3 enzymes, ophidianl-amino acid oxidase, ATPpyrophosphatase, and acetylcholinesterase, some of the problems pertaining to venom toxicity are discussed.

Potentiating effect of iproniazid on action of some sympathicomimetic amines.

Conclusions The toxic action of phenylethylamine and tyramine, but not of ephedrine and D-a-methylphenylethylamine is increased by pretreating guinea pigs with iproniazid. Isoniazid is less effective. The results are explained by the blocking of MO by iproniazid.

Enzymology of the refractory media of the eye. IV. Direct photometric determination of cholinesterase and aliesterase of corpus vitreum

Abstract On the basis of marked differences in optical density between phenol and phenyl acetate, a quasi-continuous and direct photometric method for the analysis of aliesterases and acetylcholinesterases (e-ChE) has been developed. Some properties and optimal measuring conditions of esterase of cattle corpus vitreum (c.v.), which belongs to the homologous group of acetylcholinesterases, are described.

The effect of some sympathicomimetic amines and enzyme blocking agents on asthma in the guinea pig induced by antigen or histamine aerosols

Abstract 1.1. The inhibition of the epinephrine-destroying enzyme, monoamine oxidase, by iproniazid, thus making more exogenous or endogenous epinephrine available, does not influence the asthma in the guinea pig produced by a histamine aerosol. This confirms our previously reported findings. 2.2. The inhibition of a histamine-destroying enzyme, diamine oxidase (histaminase), by isoniazid, thus making more exogenous or endogenous histamine available, does not increase the asthma produced in guinea pigs by a histamine aerosol. 3.3. The antituberculous drug pyruvic acid isonicotinoyl hydrazone, which has little inhibiting action on either monoamine oxidase or diamine oxidase, increased the tolerance of the animals to the histamine aerosol. The mechanism is unexplained. 4.4. Amines related to epinephrine (phenylethylamine, amylamine, and Tyramine) had no influence on asthma produced by aerosols of histamine or antigen. 5.5. The pretreatment of the animals with iproniazid, which inhibits the action of monamine oxidase, destroying these amines more completely than it does epinephrine, failed to affect the influence of the asthma-inducing aerosols. 6.6. The protection against asthma produced by intraperitoneal injection of ephedrine was not enhanced by pretreatment with iproniazid. 7.7. Since Benadryl is also a moderate inhibitor of monoamine oxidase, its action in preventing histamine-induced asthma might be explained on that basis. The addition, however, of iproniazid in Benadryl-treated animals failed to potentiate the action of the latter. This supports the belief that the antiallergic action of Benadryl does not depend on monoamine oxidase. 8.8. The experiments herein described together with those previously reported by us lead to the conclusion that the action of monoamine oxidase cannot be the only mechanism in the prevention of anaphylaxis in the guinea pig. 9.9. Evidence is presented which indicates that the role of endogenous diamine oxidase (histaminase) in the regulation of histamine shock in the guinea pig is negligible.

ON THE PHYSICO-CHEMICAL CHARACTERIZATION OF MONOAMINE OXIDASE (MAO) AS A BASIS FOR THE STUDY OF ITS ROLE IN PHYSIOLOGICAL AND PATHOLOGICAL PROCESSES

Publisher Summary This chapter discusses the physico-chemical characterization of monoamine oxidase (MAO) as a basis for the study of its role in physiological and pathological processes. MAO affects the reaction rates of several other components and, thus, influences the biological action of monoamines. The rate of MAO itself is the resultant of a long list of parameters such as the rates of substrate transfer to the enzyme through the outer mitochondrial membrane and the chemical nature and geometry of the enzyme and of the substrates. If the two substrates, oxygen and amine, form ternary complexes with MAO, then some substrate properties determine the affinity of MAO for oxygen and thus again the overall reaction rate in situations of low oxygen tension. As MAO inhibitors have become such important investigative tools, their mode of action needs to be understood that in turn requires substantial information about the enzyme–substrate interaction.

On the physico-chemical characterization of monoamine oxidase (MAO) as a basis for the study of its role in physiological and pathological processes

Publisher Summary This chapter discusses the physico-chemical characterization of monoamine oxidase (MAO) as a basis for the study of its role in physiological and pathological processes. MAO affects the reaction rates of several other components and, thus, influences the biological action of monoamines. The rate of MAO itself is the resultant of a long list of parameters such as the rates of substrate transfer to the enzyme through the outer mitochondrial membrane and the chemical nature and geometry of the enzyme and of the substrates. If the two substrates, oxygen and amine, form ternary complexes with MAO, then some substrate properties determine the affinity of MAO for oxygen and thus again the overall reaction rate in situations of low oxygen tension. As MAO inhibitors have become such important investigative tools, their mode of action needs to be understood that in turn requires substantial information about the enzyme–substrate interaction.