Proteins helminths

LBPs are likely to have conventional roles in the energy metabolism and transport of lipids in nematodes for membrane construction, etc. Many parasitic helminths have deficiencies in the synthesis of some lipids and so their lipid acquisition, transport and storage mechanisms clearly need to be specialized and therefore pertinent to the host-parasite relationship (Barrett, 1981). From a practical point of view, lipid transporter proteins may also be important in the delivery of anthelmintic drugs to their target most anthelmintics are hydrophobic and if they do not distribute to their site of action within the parasites by simple diffusion across and along membranes, then the parasite s own carrier proteins may be involved. 

The remaining major classes of water-soluble lipid transporter proteins (other than the polyproteins of nematodes see below) come from plants and helminths. Plants possess very small (approximately 9 kDa) helix-rich, fatty-acid-binding proteins, the structures of some of which are known (Lerche and Poulsen, 1998). A recently described class comes from cestodes these are also very small (approximately 8 kDa), presumably intracellular, and helix-rich, and bind anthelmintic drugs in addition to fatty acids (Janssen and Barrett, 1995 Barrett et al., 1997). The only helix-rich small (approximately 14 kDa) lipid transporter from vertebrates is the acetyl-CoA-binding protein (Kragelund et al., 1993). 

Delcroix, M., Sajid, M., Caffrey, C.R., Lim, K.-C., Dvorak, J., Hsieh, I., Bahgat, M., Dissous, C., and McKerrow, J.H. (2006) A multienzyme network functions in intestinal protein digestion by a platy-helminth parasite./. Biol. Chem. 281, 39316-39329. 

Adverse reactions tend to occur within a few hours of administration. They include gastrointestinal intolerance with nausea, vomiting, and abdominal discomfort. This may be due to the liberation of helminth proteins from dead worms rather than any direct effect of the drug. 

Mechanism of Action A benzimidazole carbamate anthelmintic that degrades parasite cytoplasmic microtubules, irreversibly blocks cholinesterase secretion, glucose uptake in helminth and larvae (depletes glycogen, decreases ATP production, depletes energy). Vermicidal. Therapeutic Effect Immobilizes and kills worms. Pharmacokinetics Poorly and variably absorbed from GI tract. Widely distributed, cyst fluid and including cerebrospinal fluid (CSF). Protein binding 70%. Extensively metabolized in liver. Primarily excreted in urine and bile. Not removed by hemodialysis. Half-life 8-12 hr. 

Tendler, M., Brito, C.A., Vilar, M.M., Serra-Freire, N., Diogo, C.M., Almeida, M.S., Delbem, A.C., Da Silva, J.F., Savino, W., Garratt, R.C., Katz, N. and Simpson, A.S. (1 996) A Schistosoma mansoni fatty acid-binding protein, Sm1 4, is the potential basis of a dual-purpose anti-helminth vaccine. Proceedings of the National... 

Bentley, G., Gutsmann, V., Pasi, J. and Agnew, A. (2002) Characterisation of a schistosome anti-coagulant protein, SAP. Molecular and Cellular Biology of Helminth Parasites Conference, September 2002, Hydra, Greece. 

In accordance with their opportunistic way of life, parasitic flatworms have limited biosynthetic capacities as described in Introduction, they obtain many simple substrates from their hosts. More complex molecules that the parasite cannot obtain directly from the host are synthesized from these simpler building blocks. Obviously, the parasite has to synthesize complex structures like proteins and DNA. In general, the biosynthetic pathways of parasitic helminths bear a close resemblance to those of their mammalian hosts. However, the enzymes of these pathways often possess different properties, and in cases where parasites produce unique end products, there may be distinct pathway components that involve unique enzymes that are absent from the host. 

Anikieva, L. V. Lutta, A. S. (1977). [Stored nutrients at different stages of the development of Proteocephalus exiguus La Rue, 1911 and Diphyllobothrium latum (L., 1758)]. In Russian. In Comparative biochemistry of fish and their helminths. Lipids, enzymes, proteins. (Collected works), ed. V. S. Sidorov, pp. 116-27. USSR Akademii Nauk, Institut Biologii Karel ski Filial USSR. [HA/50/3943]. 

Eosinophils are leukocytes that contain characteristic cationic proteins in their granules that bind the acidic dye eosin. In contrast to neutrophils, eosinophils are minority cells in the blood and are predominantly tissue-dwelling cells found at sites in contact with the environment the mucosal surfaces of the lung, gastrointestinal tract, and genitourinary tract. Selective accumulation of eosinophils, as opposed to neutrophils, is one of the major pathological features of the inflammatory response to infection with parasitic helminths, and in several diseases such as asthma, allergic rhinitis, and atopic dermatitis. A key step in leukocyte recruitment is the local production of chemoattractant molecules that orchestrate the adhesive interactions between leukocytes and the vascular endothelium. 

The economic losses incurred by helminth infections have been assessed in several ways. In ascariasis the loss is due to the carbohydrate depletion by Ascaris worms in the patients. It has been estimated that a patient with 20 adult worms of Ascaris lumbricoides may lose 2.8 g of carbohydrate daily [8] which amounts to 2800 kg of carbohydrate per 1 million cases per day. Thus the world-wide loss of carbohydrate for 1100 million patients carrying ascariasis would be nearly 3080 tonnes per day, Stephenson and coworkers [9] have shown that ascariasis is not only associated with poor growth and protein-caloric malnutrition in pre-school children, but also reduces absorption of macronutrients and vitamin A. The authors also showed that economic loss due to ascariasis in Kenya in 1976 was about US 5 million which could have been saved by the use of an anthelmintic costing about US 1 million only. 

A few other less studied biochemical approaches such as purine and pyrimidine metabolism protein biosynthesis and lipid metabohsm in helminths also provide targets for antiparasitic drug design [83]. Like protozoal parasites, some helminths such as S. mansoni (adult and larval forms) lack de novo purine biosynthesis and, therefore, depend entirely on the salvage mechanism for their purine requirements. Similarly amino acid metabolism and biosynthesis of proteins has also been not worked out in many parasites [83a]. Although the helminths meet their requirements of amino acids by absorbing freely from the host, they may also synthesize some amino acids. For example. Fasciola hepatica, schistosomes and other trematodes produce proline by a reaction sequence given in Chart 8. Similarly H. diminuta can... 

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