Protein venom

In this chapter, we will limit ourselves to non-proteinous poisons produced by either the venom or Dufour glands. Information on proteinous venoms can be found in the review of Schmidt [111] and the book of Blum [4]. 

Histamine may be released from mast cells by mechanisms that do not require prior sensitization of the immune system. Drugs, high-molecular-weight proteins, venoms, and other substances that damage or disrupt cell membranes can induce the release of histamine. Any thermal or mechanical stress of sufficient intensity also will result in histamine release. Cytotoxic compounds, may release histamine as the result of disruption of cell membranes. 

Proteins can also be dangerous or unhealthy. For many who suffer from allergies to agents like pollen, it is proteins on the surface of the pollen that cause an immune response that triggers the allergic reaction. More seriously, many natural toxins are proteins. Snake venom is one example of a naturally occurring protein-based toxin, see also Active Site Amino Acid Denaturation Enzymes Fibrous Proteins Globular Proteins Neurotransmitters Peptide Bond Protein Solubility Protein Synthesis Protein Translation RNA Synthesis Secondary Structure Tertiary Structure Transmembrane Proteins Venom. 

The classes of Medusozoa have been well studied, although the publications that have appeared have been largely restricted to two particularly important categories of proteins venoms and photoproteins, such as aequorin (see below and Chapter 4). There have been few studies on the lipids and secondary metabolites of Medusozoa, but an atypical series of anthracene derivatives has been isolated from the hydrozoan Garveia annulata (see below). 

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... 

Protective and exploitive proteins Immunoglobulins Thrombin Eibrinogen Antifreeze proteins Snake and bee venom proteins Diphtheria toxin Rtcin... 

Hymenoptera venoms are composed of biogenic amines and other low molecular weight substances, of basic peptides and of proteins. Injection of venom by Hymenoptera stings has toxic effects, due to biogenic amines, peptides and proteins biogenic amines such as histamine cause pain, are vasodilatory and increase... 

Venom collection is done by electrostimulation in honey bees [8] and by venom sac extraction in vespids [9]. While electrostimulation results in pure venom, venom sac extracts may be contaminated by some body proteins. The amoimt of venom injected by a sting varies from 50 to 140 pg dry weight for the honey bee, but was estimated to be much lower in vespids 1.7-3.1 pg for Vespula, 2.4-5 pg for Dolichovespula, and 4.2-17 pg for Polistes [10]. 

The venom of the Australian jack jumper ant M. pilosula has only been analyzed for its allergen composition in recent years. Besides three low molecular weight allergens, Myr pi, Myr p2 and Myr p3 (table 1), six higher molecular weight allergens of 22.8-89.9 kDa have been identified by Western blot [19]. Myr pi, a 25.6- and a 89.9-kDa protein could be major allergens. 

Hoffman DR, Jacobsen RS Allergens in Hymenoptera venoms. XII. How much protein is in a sting Ann Allergy 1984 52 276-278. 

Phospholipase A activity was subsequently demonstrated to be present in venom, and it too required Ca (25). DEAE-cellulose fractionation yielded four proteins, two of which were phospholipase A and hemolytic, and two of which had neither phospholipase A nor hemolytic activities. Either of the latter two proteins enhanced to various degrees the hemolytic activity of either of the two phospholipases. The findings suggest considerable analogy with synergistic mechanisms underlying the hemolytic action of the venoms of a number of snakes. 

All evidence indicates that the fish venoms are composed of proteins. 

There is 5-hydroxytryptamine in weever fish venom besides protein. It is believed that local pain is attributed to the presence of 5-hydroxytryptamine (27). Other small compounds such as histamine, adrenaline, and noradrenaline are also present in the weever fish (28). 

Spine venom of catfish, Ictalunis catus, contains toxins with a molecular weight of 10,000 and isoelectric points of 3.8 and 7.8 (30). Pectoral venom of Arius thal-lasinus contains alkaline phosphatase (57). The venom is a mixture of at least 30 proteins. 

From this brief review of marine vertebrate venoms, it is obvious that very few biochemical investigations have been done. The technology to study marine vertebrate venom components is available. There are simply not enough scientists interested enough to enter the field. The first task is to isolate the toxic principles and identify the amino acid sequences. Pharmacological investigation should be done on the purified toxic principle and not on the crude venom, which is a mixture of many proteins and nonproteins. 

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. 

Fig. 12.5. Schematic summary of the eight T. canis proteins containing predicted SXC (NC6) domains. The consensus is shown in the N-terminal domain of PEB-1 (phosphatidylethanolamine-binding protein-1) as xCxDxxxDC(6x)C(11x) RCxxTCxxC. This consensus is faithfully repeated in MUC-1 (mucin-1), MUC-2, MUC-4 and MUC-5, and in all but the C-terminal domain of MUC-3. This domain (and the C-terminal SXC domain of PEB-1) show consensus spacing but some variation in consensus residues. Two additional proteins with quadrupled SXC domains differ in spacing between cysteines-2, -3 and -4, and show more variation in consensus residues. These are VAH-1 (venom allergen homologue) and HUF-001 (homologue of unknown function-001).

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