Sea snake venom

Neurotoxins present in sea snake venoms are summarized. All sea snake venoms are extremely toxic, with low LD5Q values. Most sea snake neurotoxins consist of only 60-62 amino acid residues with 4 disulOde bonds, while some consist of 70 amino acids with 5 disulfide bonds. The origin of toxicity is due to the attachment of 2 neurotoxin molecules to 2 a subunits of an acetylcholine receptor that is composed of a2 6 subunits. The complete structure of several of the sea snake neurotoxins have been worked out. Through chemical modification studies the invariant tryptophan and tyrosine residues of post-synaptic neurotoxins were shown to be of a critical nature to the toxicity function of the molecule. Lysine and arginine are also believed to be important. Other marine vertebrate venoms are not well known. 

There are many venomous marine vertebrates in the seas, notably sea snakes and fishes. Venoms of sea snakes have been studied much more thoroughly than fish venoms. In this chapter, sea snake venom is described in greater detail than fish venoms simply because there is much more scientific information available. 

All sea snakes are poisonous and their venoms are extremely toxic. The LD q for crude sea snake venom can be as low as 0.10 fig/g mouse body weight (i). For purified toxin the LD q is even lower, suggesting the high toxicity of sea snake toxins and venoms. This toxicity is derived from the presence of potent neurotoxins. Compared to snake venoms of terrestrial origin, sea snake venoms have been studied less. Different enzymes reported to be present or absent are summarized in Table I. 

Before discussing the structure of the neurotoxins, it is necessary to define the types of neurotoxins. Three types of neurotoxins have been found so far in snake venoms. The first one is a postsynaptic neurotoxin, the second is a presynaptic neurotoxin, and the last is a cholinesterase inhibiting neurotoxin. Most sea snake venoms seem to contain only the postsynaptic neurotoxin. Only in Enhydrina... 

Table I. Presence and Absence of Enzymes in Sea Snake Venoms...

Another type of neurotoxin found in sea snake venoms is a hybrid type structurally situated between the short-chain and long-chain types. As can be seen in Table IV, two toxins shown here have a long stretch of segment 4, yet there is no disulfide bond in this portion. 

The similarity of the primary structure of different sea snake venoms has already been discussed. Postsynaptic neurotoxins from Elapidae venom have been extensively studied. Elapidae include well-known snakes such as cobra, krait, mambas, coral snakes, and all Australian snakes. Like sea snake toxins, Elapidae toxins can also be grouped into short-chain (Type I) and long-chain (Type II) toxins. Moreover, two types of neurotoxins are also similar to cardiotoxins, especially in the positions of disulfide bonds. However, amino acid sequences between cardiotoxins and sea snake and Elapidae neurotoxins are quite different. In comparing the sequence of sea snake and Elapidae neurotoxins, there is a considerable conservation in amino acid sequence, but the difference is greater than among the various sea snake toxins. 

Similarity of venoms among different sea snakes and Elapidae can also be detected immunologically. For instance, the antibody for Enhydrina schistosa showed cross reactivity with the venoms of Hydrophis cyanocinctus, Lapemis hardwickii, and Pelamis platurus 12). The sea snake antivenin not only neutralizes the toxicity of various sea snake venoms, but also Naja naja atra (Taiwan cobra) venom 13-16). The reverse is also true namely, some Elapidae antivenins are also effective for neutralizing sea snake venom lethality 17-19). 

Since sea snake venoms are discussed here, it is appropriate to review other vertebrate venoms also. Unfortunately, very few investigations have been done on the venoms of other marine vertebrates. It is known that some fish secrete venoms from their spines. The fishes known to have venoms are the scorpion fish (family Scorpaenidae), weever fish (family Trachinidae), catfish (order Siluriformes there are 31 families), stargazers (family Uranoscopidae), toad fish (family Batrachoidi-dae), and stingrays (suborder Myliobatoidea). 

Lee CY, Chang CC, Chen YM (1972) Reversibility of neuromuscular blockade by neurotoxins from elapid and sea snake venoms. Taiwan Yi Xue Hui Za Zhi 71 344-9 Lee CY, Tsai MC, Chen YM, Ritonja A, Gubensek F (1984) Mode of neuromuscular blocking action of toxic phospholipases A2 from vipera ammodytes venom. Arch Int Pharmacodyn Ther 268 313-24... 

Tamiya, N. 1975. Sea snake venoms and toxins. In The Biology of Sea Snakes, ed. W.A. Dunson, pp. 386-415, University Park Press, Baltimore. 

Tu, A.T. (1974a) Sea snake venoms and neiuotoxins. /. Agric. Food Chem., 22, 36-43. 

Tu, A. T., and Toom, P. M. (1971). Isolation and characterization of the toxic components of Enhydrina schistosa (common sea snake) venom. J. Biol. Chem. 246 1012-1016. 

Snake neurotoxins are the main toxic proteins of cobra, krait, tiger snake and sea snake venoms which block neuromuscular transmission and cause animals death of respiratory paralysis. Snake neurotoxins are classified into two distinct types, postsynaptic and presynaptic neurotoxins, in relation to the neuromuscular junction. Postsynaptic neurotoxins bind specifically to nicotinic acetylcholine receptor (AChR) at the motor endplate and produce a nondepolarizing block of neuromuscular transmission. Presynaptic neurotoxins block the release of acetylcholine from the presynaptic motor nerve terminals. 

To date, more than 120 toxins with neurotoxic activity have been isolated in pure state from elapid and hydrophid (sea-snake) venoms. Over 100 highly homologous postsynaptic neurotoxins belonging to two distinct size groups, short and long neurotoxins, have been sequenced (Yang, 1974,1984 Mebs, 1988 Endo and Tamiya, 1991). Short neurotoxins contain 60-62 amino acid residues with four disulfide bonds, and long neurotoxins comprise... 

Other Lethal Agents. There are a number of substances, many found in nature, which are known to be more toxic than nerve agents (6). None has been weaponized. Examples of these toxic natural products include shellfish poison, isolated from toxic clams puffer fish poison, isolated from the viscera of the puffer fish the active principle of curare "heart poisons" of the digitaUs type the active principle of the sea cucumber active principles of snake venom and the protein ricin, obtained from castor beans (See Castor oil). 

Neurotoxins from Sea Snake and Other Vertebrate Venoms... 

While most investigations show that sea snake neurotoxins are postsynaptic type, Gawade and Gaitonde (23) stated that Enhydrina schistosa major toxin has dual actions or postsynaptic as well as presynaptic toxicity. E, schistosa venom phospholipase A is both neurotoxic and myotoxic. Neurotoxic action of the enzyme is weak so that there is sufficient time for myonecrotic action to take place (24), Sea snake, L. semifasciata toxin also inhibits transmission in autonomic ganglia, but has no effect on transmission in choroid neurons. 

Aposematically colored, the yellow-bellied sea snake, Pehmis platurus (Hydrophiidae), of the eastern Pacific has venom and is distasteful. It has no known aquatic predators, although remains were found in murray eels and sharks. Predatory fish such as snappers refuse the snake. They reject its meat even when hidden in palatable squid. Predatory fish of the Atlantic ocean, however, ate the sea snake in experiments, and died after 1 of 12 meals (Rubinoff and Kropach, 1970). 

The clinical features depend upon the type of snake bite. There are three main patterns neurotoxic, as with elapidae such as cobras and kraits vasculotoxic with alteration in blood coagulation as with vipers and myotoxic as with sea snakes although they are all often complicated by local tissue damage. The severity of poisoning will depend on the amount and potency of venom injected and the patient s general health. 

Sea Snakes in Australian Waters. CRC Reef Research Centre. Available online. URL http //www.reef.crc.org.au/discover/plantsanimals/seasnakes. Accessed November 18, 2004. An overview of sea snake classification, breeding, and venom. 

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