Snake venom enzymes

SNAKE VENOM ENZYMES HYDROLASES THAT PRODUCE TOXIC EFFECTS... 

K. Stocker. Deflbrinogenation with tbrombinlike snake venoms enzymes. Inc Handbook of Experimental Pharmacology, VoL 48 (F. Maikwnrdi, ed.). Springer, Berlin, 1977, pi 451,... 

Nucleoside Pyrophosphates. - 2.3.1 Nucleoside Diphosphate Analogues. A large variety of esters with different nucleoside and alkyl moieties (llla-j) have been synthesised in small amounts using different combinations of nucleoside triphosphate, alcohols and snake venom pyrophosphatase. Potato tube pyrophosphatase was also reported as being a possible practical biocatalyst to synthesise such nucleotide pyrophosphate-O-alkyl esters, but using more stringent reaction requirements than that of the snake venom enzyme. ... 

The third type of enzyme presumably involved in degradation of the polymer is phosphodiesterase. The snake venom enzyme has been used extensively to degrade the polymer for structural anedysis. The nuclear phosphodiesterase from liver will hydrolyze the pyrophosphate bonds of poly(ADP-ribose), NAD, NADH, and ADP-ribose 135). Futai has demonstrated that the hydrolysis of poly( ADP-ribose) proceeds from the AMP terminus 71) (refer to Fig. 4). 

The stoichiometry of the release of peptides A and B is illustrated in Fig. 73. For example, bovine fibrinogen contains six chains, two each having N-terminal glutamic acid and tyrosine, respectively, and two chains with no detectable N-terminal group. Papain and snake venom enzyme split two bonds with a release of only peptide A and produce a clottable material... 

It appears that most nucleotide pyrophoqihatases from mammalian tissues cleave the reduced forms of the coenzymes faster than the oxidized nucleotides. The plant nucleotide pyrophosphatases, however, q>lit DPNH, TPNH, and the oxidized coenzyme forms at equal rates. It should be pointed out, however, that an enzyme such as the potato nucleotide pyrophosphatase also attacks ATP and adenosine diphosphate (ADP), whereas the purified pigeon liver enzyme does not. The snake venom enzyme seems to split the oxidized and reduced nucleotide at equal rates. 

Snake Venoms, Enzymes of, Biologieed Significance (Zeller). VIII 459... 

Lysolecithins and lysocephalins are produced by the hydrolytic action of snake-venom enzymes (cf. Section 3). These products have only one fatty acid residue left the hydroxyl group in /3-position is free. 

Itoh, N., Tanaka, N., Mihashi, S., and Yamashina, I. (1987). Molecular cloning and sequence analysis of cDNA for batroxobin, a thrombin-like snake venom enzyme. J. Biol. Chem. 262 3132-3135. 

Markland, F.S., Morris, S., Deschamps, J.R. and Ward, K.B., 1993, Resolution of isoforms of natural and recombinant fibrinolytic snake venom enzyme using high performance capillary electrophoresis, J. Liquid Chromatog. 16 2189-2201. 

Hydrolytic enzymes phospholipases in snake venoms, endogenous... 

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. 

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. 

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

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. 

The bearing which these discoveries have had on the elucidation of the structure of ribopolynucleotides will be discussed later. It is important to stress here, however, that, for most purposes, the older methods of preparing nucleotides have been superseded by procedures which yield separate isomers of each. Of the techniques mentioned above, paper chromatography iB mainly of analytical value, and is the most convenient method for the qualitative detection of isomeric adenylic acids. The only disadvantage of this method is that the isomers are not completely separable from muscle adenylic acid. The presence of the latter, however, can be readily detected by hydrolyzing it to adenosine by means of the specific 5-nucleotidase present in snake venoms,66 or by deamination by a specific enzyme... 

Hydrolysis of ribonucleic acids by snake venom was found to yield inorganic phosphate, nucleosides, and pyrimidine ribonucleoside diphosphates.197 These diphosphates were shown by their behavior toward various enzymes to be mixtures of 2,5- and 3,5-diphosphates, and it therefore seems likely that they were formed through intermediate, cyclic phosphates. Thus, although this evidence confirms the existence of 2(or 3) — 5 linkages, it does not distinguish between the 2- and 3-positions. 

D-Amino acid oxidase (EC 1.4.3.3) extracted from sheep kidney possesses low selectivity and at pH 8-9 will oxidise many D amino acids, whereas L-amino acid oxidase (EC 1.4.3.2) from snake venom (Crotalus adaman-teus) at pH 8-9 catalyses the oxidation of many L amino acids. However, as these enzymes show different reactivity towards different amino acids, the results for a sample that contains several D and L amino acids may be difficult to interpret. The use of these enzymes is therefore only recommended for the measurement of one isomer of an isolated amino acid. They may also be used to remove an unwanted isomer from a sample containing both to allow subsequent measurement of the other. 

Using phosphotriester methods, dinucleoside (3 - 50-monophosphates containing 6-methyl-2,-deoxyuridine at the 3 - or 5 -end have been prepared.44 N.m.r. spectroscopy indicates that this nucleoside possesses the syn conformation in these compounds, and, on treatment with snake venom phosphodiesterase, d(m6UpT) is degraded, while d(Apm6U) is not, indicating that this enzyme, a 3 -exonuclease, requires the anti conformation to be present in the substrate. Two modified nucleo-side-5 -monophosphates, (20) and (21), which are resistant to 5 -nucleotidase, have been isolated from tRNA snake venom hydrolysates.45 A synthesis of (20) has been reported.46... 

Unless the last-mentioned product is removed by the inclusion of catalase, the oxoacid is liable to react further, undergoing oxidative decarboxylation to the carboxylic acid. An attractive feature of this group of enzymes in the present context is that there exist readily available representatives of both enantiospecificities. The well-studied and commercially available AAOs from vertebrate sources, such as l-AAO from snake venom and D-AAO from pig kidney, are expensive, however, and are increasingly being replaced by enzymes from microbial sources. 

Since predators of snakes (and humans) have to deal with snake venoms as defenses, they are included here, even though they serve in predation. Snake venoms are primarily enzymes (proteins), especially of the phospholipase A2 type, which breaks down cell membrane phospholipids hydrolytically. Other snake venoms such as cobrotoxin contain peptides with 60-70 amino acid residues. Pharmacologically, they have neurotoxic, cytotoxic, anticoagulant, and other effects. The neurotoxins, in turn, can have pre- or postsynaptic effects. Snake venoms with both neurotoxic and hemolytic effects on the heart are known as cardiotoxins. Cytotoxins attach to the cells of blood vessels and cause hemorrhage. Snake venom factors may stimulate or inhibit blood clotting. Finally, platelet-active factors can contribute to hemorrhage. 

Snake venoms are composed of a toxic mixture of enzymes that can kill or immobilize prey. 

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