Sea snakes

Neurotoxins from Sea Snake and Other Vertebrate Venoms... 

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. 

The sea snake is a marine-adapted serpent belonging to the family of Hydrophi-idae. There are many varieties of sea snakes with different colors, shapes, and sizes. They are well adapted for the marine environment and have a flat tail and a salt gland. Sea snakes are widely distributed in tropical and subtropical waters along the coasts of the Indian and Pacific Oceans. They are not found in the Atlantic Ocean. 

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. 

It is a supposition that the )9-sheet structure of neurotoxin is an essential structural element for binding to the receptor. The presence of -sheet structure was found by Raman spectroscopic analysis of a sea snake neurotoxin (2). The amide I band and III band for Enhydrina schistosa toxin were at 1672 cm and 1242 cm" respectively. These wave numbers are characteristic for anti-parallel -sheet structure. The presence of -sheet structure found by Raman spectroscopic study was later confirmed by X-ray diffraction study on Laticauda semifasciata toxin b. 

Sea snake short-chain toxins have a molecular weight of only 6,800. The small size with four disulfide bonds makes these toxins very compact and stable molecules. Therefore, when the Pelamis platurus toxin is subjected to heat treatment at 100 C and subsequent cooling, it does not change its conformation substantially. Amide I and ni bands and S-S stretching vibration did not change by heat treatment. 

The one residue most extensively studied is tryptophan. It is very easily modified, indicating that tryptophan residue is exposed 5-8). Raman spectroscopic analysis of a sea snake neurotoxin indicated that a single tryptophan residue is indeed exposed (2). The tryptophan residue lies in the important loop consisting of segment 4. Modification of the tryptophan residue induces the loss of AChR binding ability as well as the loss of toxicity 5-8). 

There is only one tyrosine residue in some sea snake neurotoxins. This residue is usually quite difficult to modify, but once it is modified, the toxicity is lost (9). Histidine seems not to be essential as the chemical modification of this residue does not affect the toxicity 10). 

Argine and lysine are believed to be important, but results are not clear because sea snake neurotoxins contain several residues of these amino acids (7). 

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). 

When a nerve-muscle preparation is stimulated in the presence of a sea snake neurotoxin, there is no twitch. However, when the muscle itself is stimulated directly in the presence of a neurotoxin, the muscle contracts. This means that neurotoxin does not inhibit the muscle itself. Moreover, postsynaptic neurotoxin does not inhibit the release of acetylcholine from the nerve ending. Therefore, the site of snake toxin inhibition must be in the postsynaptic site 20). Later it was shown that a neurotoxin strongly binds to the acetylcholine receptor (AChR). 

Table II. Amino Acid Sequence of Sea Snake Neurotoxins (Type I or Short Chain)...

Table III. Amino Acid Sequences of Sea Snake Neurotoxin (T>pe II, Long Chain)...

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. 

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). 

Cobra (Walkinshaw et ah, 1980), see Erabutoxin Sea snake (Tsernoglou and Petsko, 1977), see Erabutoxin Nuclease, staphylococcal (or micrococcal) (Arnone et ah, 1971) Greek key /3 barrel (Fig. 80)... 

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). 

Rubinoff, I. and Kropach, C. (1970). Differential reactions of Atlanticand Pacific predators to sea snakes. Nature 228,1288-1290. 

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. 

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... 

Base treatment of helical biliverdins with 2-chloroethyl side chains leads to intramolecular rearrangement to yield derivatives with extended conformations <89JAI525>. This work has been extended to include inter alia the syntheses of Neobiliverdin Ixd (26), a natural product from the ovaries of the sea snake Turbo cornutus, by reaction of (25) with base <95T2243,2255>. 

Ten per cent of the snakes in the world, about 300 different species, are poisonous, and snakes are an important source of natural toxins. Poisonous snakes belong primarily to certain groups, such as that including the mamba and cobra, the vipers, and the sea snakes and another group that includes the boomslang and the mangrove. 

Sea snakes (family Hydrophiidae) are close relatives of the cobra, coral, and other snakes belonging to the... 

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