Chapter 26

• Venomous animals produce poison in a highly developed secretory gland or group of cells and can deliver their toxin during a biting or stinging act.
• Poisonous animals are those whose tissues, either in part or in their entirety, are toxic. Poisoning usually takes place through ingestion.
• The bioavailability of a venom is determined by its composition, molecular size, amount or concentration gradient, solubility, degree of ionization, and the rate of blood flow into that tissue as well as the properties of the engulfing surface itself.
• The distribution of most venom fractions is rather unequal, being affected by protein binding, variations in pH, and membrane permeability, among other factors.
• A venom may also be metabolized in several or many different tissues.
• Because of their protein composition, many toxins produce an antibody response; this response is essential in producing antisera.

Venomous animals are capable of producing a poison in a highly developed exocrine gland or group of cells and they can deliver their toxin during a biting or stinging act. Poisonous animals have no mechanism or structure for the delivery of their poisons, and poisoning usually takes place through ingestion.

Venoms are very complex, containing polypeptides, high- and low-molecular-weight proteins, amines, lipids, steroids, glucosides, aminopolysaccharides, quinones, and free amino acids, as well as serotonin, histamine, and other substances. The complexity of snake venoms is illustrated in Figure 26–1.

###### Figure 26–1

Components of snake venoms. ACE = angiotensin-converting enzyme; CRISP = cysteine-rich secretory protein; CVF = cobra venom factor-like proteins; LAO = l-amino acid oxidase; PLA2 = phospholipase A2; RGD = arginine–glycine–aspartate. (Reprinted with permission from Ramos OHP, Selistre-de-Araujo HS: Snake venom metalloproteases—structure and function of catalytic and disintegrin domains. Comp Biochem Physiol, Part C 142:328–346, 2006. Copyright © Elsevier.)

Novel instrument developments have permitted researchers to tease out the complexity of natural venoms, thereby identifying the peptide and protein components of venom. Unfortunately, studying the chemistry, pharmacology, and toxicology of venoms requires isolating and dismantling the venoms and losing the synergy among multiple components. Nevertheless, advanced technology will permit peptide sequencing and the characterization of post-translational modifications, such as glycosylation, and the discovery of new pharmacophores.

Venom bioavailability is determined by its composition, molecular size, amount or concentration gradient, solubility, degree of ionization, and the rate of blood flow into that tissue as well as the properties of the engulfing surface itself. The venom can be absorbed by active or passive transport, facilitated diffusion, or even pinocytosis. It is then transmitted into the vascular bed, sometimes directly or sometimes through lymphatic channels. The lymph circulation not only carries surplus interstitial fluid produced by the venom, but also transports the larger molecular components and other particulates back to the bloodstream.

The site of action of venom is dependent on its diffusion and partitioning ...

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