Botulinum toxin is produced by Clostridium botulinum, a gram-negative bacterium.

Question

Botulinum toxin is produced by Clostridium botulinum, a gram-negative bacterium. The toxin actually consists of 7 related toxins, types A, B, C1, D, E, F, and G. The toxin is synthesized as a protoxin of 150kDa, which is proteolytically cleaved to light (L) and heavy (H) chains that remain linked by a disulfide bond. Nerve terminals have receptors for both L and H chains. The L-chain is transported across the nerve terminal membrane by endocytosis. The L chains are metaloproteinases - proteases that require metal ions for activity. The L-chain binds Zinc and it proteolytically degrades several proteins that make up the SNARE complex.

A) What do you suppose happens when botulinum toxin is injected near the neuromuscular junctions?

B) From this conclusion, what do you suppose the basis for botox injections?

Explanation / Answer

A. Botulinum toxin has a light chain and a heavy chain, each of which contributes to the toxicity. The heavy chain allows the protein to bind to and enter a neuron. After the heavy chain allows entry, the light chain acts like a protease and cleaves proteins that would normally allow neurotransmitters to leave the cell. This is essentially a disruption of exocytosis or the release of neurotransmitters. The blocked neurotransmitter, Acetylcholine, normally transmits a nerve impulse to a muscle, signaling the muscle to contract. By blocking this neurotransmitter, botulinum toxin causes its characteristic flaccid paralysis.

B. When used in a medical setting as an injectable form of sterile, purified botulinum toxin, small doses block the release of a chemical called acetylcholine by nerve cells that signal muscle contraction. By selectively interfering with the underlying muscles' ability to contract, existing frown lines are smoothed out and, in most cases, are nearly invisible in a week.

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