Botulinum Activation mechanism

Muscle relaxation is caused by various mechanisms, such as depression of ACh synthesis (e.g, hemicholinium), storage (vesamicol) and release (magnesium, botulinum toxin) and depression of muscle activity by drugs such as dantrolene and baclofen,... 

Fig. 1. The mechanism of activation of tetanus and botulinum neurotoxins. The toxins are produced as an inactive single polypeptide chain of 150 kDa, composed of three 50 kDa domains, connected by protease-sensitive loops. The toxins are activated by selective proteolytic cleavage which generates two disulfide-linked chains L (50kDa) and H (100kDa). The three domains play different functional roles in cell penetration He is responsible for cell binding and Hn for cell penetration. Reduction takes place inside the nerve cells and liberates the metallo-protease activity of fhe L chain in the cytosol...

An alternative mechanism of the involvement of the transglutaminase catalyzed immobilization of the synaptic vesicles have been proposed for tetanus-induced blockage of the neurotransmitter release (Facchiano et al., 1993). In the past, attempts have been made to demonstrate ADP-ribosyl transferase activity in botulinum neurotoxins (cf. Singh, 1990) without any success. The hypothesis of ADP-ribosyl transferase activity of botulinum neurotoxins derives from analogies with diphtheria, cholera and botulinum C2 toxins, all with similar extracellular mode of action (Simpson, 1989b). 

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