Botulinum Toxin: A Deadly Poison Sheds Its Negative Image
- Lance L. Simpson, PhD
- Jefferson Medical College, Philadelphia, PA 19107 Grant Support: In part by National Institutes of Health grant NS-22153 and by Department of the Army contract DAMD17-90-C-0048. Requests for Reprints: Lance L. Simpson, PhD, Departments of Medicine and Pharmacology, Jefferson Medical College, 1020 Locust Street, Philadelphia, PA 19107.
Botulinum toxin is a remarkable substance. It is highly potent and can cause botulism, but it is also a highly efficacious medication that can produce clinical benefits in patients with nerve and muscle disorders. Interestingly, the underlying mechanism that causes disease is the same mechanism that provides clinical benefits.
The major source of botulinum toxin is the organism Clostridium botulinum; C. barati and C. butyricum also produce the toxin [1-3]. The toxin is synthesized in seven serotypes, designated A, B, C, D, E, F, and G. Serotypes A, B, and E account for almost all cases of human botulism. Serotype A has been approved by the Food and Drug Administration for treatment of various medical problems, and other serotypes are being evaluated in clinical trials.
Each of the seven toxin serotypes is synthesized as a single-chain polypeptide (molecular weight, 150 000) that has only minimal toxicity [4]. To become fully active, the single-chain molecule must be cleaved by proteolysis to generate a heavy chain (molecular weight, 100 000) that is linked by a disulfide bond to a light chain (molecular weight, 50 000). It is the dichain form of the molecule that causes both poisoning and therapeutic benefits.
Although humans can come into contact with botulinum toxin in several ways, two situations account for almost all outbreaks of botulism …
This 100-word excerpt has been provided in the absence of an abstract.
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