VPT 421: Veterinary Toxicology (2+0)

Action After Interaction With Target Molecule

INTERACTION WITH TARGET MOLECULE

• Due to interaction with the target molecule there can be various reactions like non-covalent binding, covalent binding, hydrogen abstraction, electron transfer and enzymatic reactions. The interaction may cause a reactivity in the target organ and also affect its critical function. The outcome of a toxicant target molecule interaction can be dysfunction, destruction or neoantigen formation.

• Noncovalent bond formation - Binding of strychnine to the glycine receptor on motor neurons in the spinal cord.
• Covalent bond formation - Carbon monoxide, cyanide, hydrogen sulfide and azide form coordinate covalent bonds with iron in various hemeproteins.
• Electron transfer - Phenolic compounds (such as 5-hydroxyprimaquine) and hydrazines (such as phenylhydrazine) are co-oxidized with oxyhemoglobin, forming methemoglobin and hydrogen peroxide.
• Enzymatic reaction - Botulinum toxin acts as a Zn-protease and hydrolyses the fusion proteins that assist in exocytosis of the neurotransmitter acetylcholine in cholinergic neurons.
• Dysfunction - Tetrodotoxin and saxitoxin, inhibit opening of the voltage-activated sodium channels in the neuronal membrane.
• Destruction - Free radicals such as Cl 3 COO • and HO • can initiate peroxidative degradation of lipids by hydrogen abstraction from fatty acids
• Neo antigen formation - Penicillin-bound proteins as antigens react with IgE-type antibodies on the surface of mast cells and this reaction triggers release of mast cell mediators (e.g., histamine, leukotrienes), which in turn may cause bronchoconstriction (asthma), vasodilatation and plasma exudation (wheal, anaphylactic shock).