Birtoxin
Category	Ion channel toxin, Neurotoxin Neurotoxin A neurotoxin is a toxin that acts specifically on nerve cells , usually by interacting with membrane proteins such as ion channels. Some sources are more general, and define the effect of neurotoxins as occurring at nerve tissue...
Species	Parabuthus transvaalicus Parabuthus transvaalicus Parabuthus transvaalicus is a species of scorpion from southern Africa. It is also known as "Dark Scorpion".-Description:P. transvaalicus grows to a length of , and is dark brown or black in colour. Its pincers are thin, but its tail is thickened, with the sting segment being as wide as the rest of...
Target	voltage-gated sodium channel
Symptoms	Lethal Lethal Lethal is an adjective meaning capable of causing death.Lethal may also refer to:* Lethal , an American heavy metal band* Leigh Matthews, Australian rules footballer nicknamed "Lethal" or "Lethal" Leigh... , tachypnea Tachypnea Tachypnea means rapid breathing. Any rate between 12-20 breaths per minute is normal. Tachypnea is a respiration rate greater than 20 breaths per minute. - Distinction from other breathing terms :... , convulsions, tremors
Taxonomic ID	170972
Sequence length	58 AA

Birtoxin is a neurotoxin from the venom of the South African Spitting scorpion

Parabuthus transvaalicus

Parabuthus transvaalicus is a species of scorpion from southern Africa. It is also known as "Dark Scorpion".-Description:P. transvaalicus grows to a length of , and is dark brown or black in colour. Its pincers are thin, but its tail is thickened, with the sting segment being as wide as the rest of...

 (Parabuthus transvaalicus). By changing sodium channel activation, the toxin promotes spontaneous and repetitive firing.

Source

Birtoxin was isolated from the venom of the South African Spitting scorpion. It is a peptide

Peptide

Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...

 that is moderately toxic but very abundant in the venom. Other peptide toxins found in the venom include: dortoxin

Dortoxin

Dortoxin is a lethal peptide toxin which is secreted by the South African spitting scorpion Parabuthus transvaalicus. Injection of pure dortoxin in mice leads to hyperactivity that lasts until death.-Source:...

, a lethal peptide; bestoxin

Bestoxin

Bestoxin is a neurotoxin from the venom of the South African spitting scorpion Parabuthus transvaalicus. Most likely, it targets sodium channel function, thus promoting spontaneous and repetitive neuronal firing...

, which causes writhing in mice; and altitoxin

Altitoxin

Altitoxin is a neurotoxin found in the South African scorpion Parabuthus transvaalicus. Injection of altitoxin in mice leads to akinesia, depression and death.-Source:...

, a highly depressant peptide.

Chemistry

Generally, peptide neurotoxins can be divided into two major families, the ‘long chain neurotoxins’ (LCN) with 60- to 70-residue range and known to contain eight cysteine

Cysteine

Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...

 residues; and the ‘short chain neurotoxins’ (SCN) with 30 to 40 peptides with six or eight cysteine residues. Birtoxin, together with other birtoxin-like peptides including bestoxin

Bestoxin

Bestoxin is a neurotoxin from the venom of the South African spitting scorpion Parabuthus transvaalicus. Most likely, it targets sodium channel function, thus promoting spontaneous and repetitive neuronal firing...

, is 58 amino-acid residues long, close to the ‘long chain’ family but with six cysteine residues. Birtoxin is reticulated by three disulfide

Disulfide

In chemistry, a disulfide usually refers to the structural unit composed of a linked pair of sulfur atoms. Disulfide usually refer to a chemical compound that contains a disulfide bond, such as diphenyl disulfide, C6H5S-SC6H5....

 bridges, instead of four, compared to other LCNs
. Therefore it is considered to be the evolutionary link between ‘long chain’- and ‘short chain’- families.

Mode of action

Birtoxin affects the gating mechanism of sodium channels by binding to neurotoxin receptor site 4 of the channel, resulting in the lowering of the voltage threshold of the channel and a reduction in the current amplitude. Due to the change in the activation the sodium channel will open at smaller depolarisations. This causes increased excitability, which leads to symptoms such as convulsions, continuous urination, tremors and tachypnea (faster breathing).

Toxicity

Birtoxin only affects mammals. No effect is found on reptiles, insects or fish. In experiments performed on mice, symptoms such as convulsions, continuous urination, tremors and tachypnea

Tachypnea

Tachypnea means rapid breathing. Any rate between 12-20 breaths per minute is normal. Tachypnea is a respiration rate greater than 20 breaths per minute. - Distinction from other breathing terms :...

 occurred 10 minutes after injection and increased during 30 minutes. An injection of 1 μg of birtoxin resulted in severe neurotoxic effects for 24 hours, but this dose is not lethal to mice. LD₉₉ in mice is achieved at 2 μg.

An antibody

Antibody

An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...

 against the N-terminus of the birtoxin protein structure has been shown to neutralize the venom of the South African spitting scorpion, and such antibodies may be useful clinically to treat envenomation

Envenomation

Envenomation is the process by which venom is injected into some animal by the bite of a venomous animal. Many kinds of animals, including mammals , reptiles , spiders , insects , employ venom for hunting and for self defense...

.