Venom snake

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). 

Figure 2.14 shows examples of both cases, an isolated ribbon and a p sheet. The isolated ribbon is illustrated by the structure of bovine trypsin inhibitor (Figure 2.14a), a small, very stable polypeptide of 58 amino acids that inhibits the activity of the digestive protease trypsin. The structure has been determined to 1.0 A resolution in the laboratory of Robert Huber in Munich, Germany, and the folding pathway of this protein is discussed in Chapter 6. Hairpin motifs as parts of a p sheet are exemplified by the structure of a snake venom, erabutoxin (Figure 2.14b), which binds to and inhibits... 

Hydrolytic enzymes phospholipases in snake venoms, endogenous... 

Snake venom plio.spliodie.stera.se an "a specific exonnclea.se ... 

Snake venom pliospliodie.stera.se attacks here next... 

FIGURE 11.31 Snake venom phosphodiesterase and spleen phosphodiesterase are exonncleases that degrade polynncleotides from opposite ends. 

Snake venom phosphodiesterase Both a Starts at 3 -end, 5 -NMP products... 

The process for preparing the enzyme composition comprises treating an aqueous solution of the snake venom at a pH of about 4 to 6 with phenol or a phenol derivative in order to precipitate an insoluble complex containing the active venom fraction and decomposing the complex in order to release the thrombinlike enzyme composition. 

II A-F Snake venom, synovial fluid, pancreas, testis, spleen, brain, heart, uterus 13-17 6-8... 

Nerve growth factor snake venoms zinc, 6, 613 Neurospora crassa calcium transport, 6, 571 cation transport, 6, 559 Neurosporin, 6, 676 Neurotransmitters secretion calcium, 6, 595 Neutral complexes electrical properties, 6, 143 Neutron absorbers... 

Harris, J.B. (1990). Phospholipases in snake venoms and their effects on nerve and muscle. In Snake Toxins (Harvey, A.L., ed.), pp. 91-129, Pergamon Press, Oxford. 

Harris, J.B., Cullen, M.J. (1991). Muscle necrosis caused by snake venoms and toxins. Electron Microsc, Rev. 3, 183-211. 

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). 

Beta-bungarotoxin, a protein in cobra snake venom, also binds to cholinergic nerves to stop ACh release while a-bungarotoxin (from the same source) binds firmly to peripheral postsynaptic nicotinic receptors. The combined effect ensures the paralysis of the snake s victim. 

Ribonucleoside 5 -0-hydroxymethylphosphonates (8 R = OH) are resistant to the action of phosphatases and phosphodiesterases. They are, however, good substrates for snake venom 5 -nucleotidase, unlike (8 R = H).2 ... 

Phosphoramidate analogues of dideoxyribonucleoside phosphates (26) and trideoxyribonucleoside phosphates are acid labile and can be hydrolysed enzymically. Snake venom phosphodiesterase cleaves (26) to thymidine and 5 -deoxy-5 -aminothymidine (27 R = H). The latter presumably arises by spontaneous decomposition of the phosphoramidate (27 R = PO3H2) and P—O fission must have occurred during the initial hydrolysis. With acid or spleen phosphodiesterase, (26) gave Tp and (27 R = H), i.e. P—N fission occurred. 

Snake venoms, neuroactive, 21 (1984) 63 Sodium cromoglycate analogues, 21 (1984) 1... 

Once injured or activated by a toxic substance (e.g., bacterial toxins, placenta chemicals, snake venom, etc.), endothelial cells and monocytes respond by generating tissue factor on the cell surface. This, in turn, leads to the generation of tissue factor-factor Villa complexes, followed by unregulated and excessive generation of thrombin, fibrin, systemic microthrombi and consumption of coagulation factors,... 

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