MadSci Network: Biochemistry
Query:

Re: What enzyme does Botox inhibit in a muscle contraction?

Date: Wed Nov 5 09:54:37 2003
Posted By: Michael Parker, Research Chemist
Area of science: Biochemistry
ID: 1067969669.Bc
Message:

Botox is the common name for botulinum neurotoxin A, a toxic protein that 
is produced by the bacterium clostridium botulinum.   It is a neurotoxin 
that causes muscle relaxation at low doses and muscle paralysis at higher 
doses.  To explain how it works, let me briefly describe the process by 
which neurons transmit signals from one to another.

Within a neuron, a nerve impulse is transmitted electrically.  However, 
between two neurons, the signal is transmitted by chemicals that are 
released into the gap between the neurons.  When these chemicals (in 
general, called neurotransmitters) are not in use, they are stored within 
synaptic vesicles – small spheres within the nerve cell.  The vesicles are 
surrounded by a thin membrane.  When a nerve impulse arrives, the vesicles 
move toward the outer membrane of the cell and make contact with it.  The 
membrane of the vesicle merges with the membrane of the cell.  For this 
fusion to occur, certain proteins must be present on the surface of the 
vesicle.  When the fusion occurs, the contents of the vesicle, the 
neurotransmitters, spill outside of the cell.  The neurotransmitters are 
then sensed by the adjacent neuron, and an electrical signal is generated 
and passed on.  

Botox is a protein that functions as an enzyme (specifically, a zinc 
endopeptidase) that cleaves another protein called synaptosomal associated 
protein or SNAP-25.  SNAP-25 is located on the surface the membranes of 
the synaptic vesicles that contain neurotransmitters.  This is one of the 
proteins that is necessary for the fusion of the vesicle with the cell 
membrane.  When botox is present, it cleaves SNAP-25 causing it to be non-
functional.  The vesicles can’t fuse with the cell membrane, the 
neurotransmitters are not released, and a nerve impulse cannot be 
transmitted from one neuron to another.  When this occurs in muscle tissue 
the end result is paralysis or at least a barrier to easy function, which 
manifests as relaxation. 

So to answer your question, if the article you read stated that “Botox 
injections inhibited the production of an enzyme that causes muscle 
contraction” this does not appear to be accurate.  A simple one-sentence 
description of how botox works might be better stated this way:  Botox is 
an enzyme which indirectly inhibits the release of neurotransmitters that 
are necessary for muscle contraction.

[Moderator's note : I believe that the primary reference for the work Michael described is :
Blasi J, Chapman ER, Link E, Binz T, Yamasaki S, De Camilli P, Sudhof TC, Niemann H, Jahn R. 
(1993) Botulinum neurotoxin A selectively cleaves the synaptic protein SNAP-25. 
Nature. 365:160-3. ]


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