Nematodes metabolism

Madin, K.A.C. Crowe, J.H. (1975). Anhydrobiosis in nematodes carbohydrate and lipid metabolism during dehydration. Journal of Experimental Zoology, 193, 335-41. 

Pyrene is metabolized by the fungus Crinipellis stipitaria to 1-hydroxypyrene, and this has a spectrum of toxic effects substantially greater than those of pyrene these include cytotoxicity to HeLa S3 cells, toxicity to a number of bacteria and to the nematode Cae-norhabditis elegans (Lambert et al. 1995). 

The parasitic nematode, Ascaris suum, undergoes a number of well-characterized metabolic transitions during its development (Table 14.1), but little is known about the regulation of these events (Barrett, 1976 Komuniecki and Komuniecki, 1995). Adults reside in the porcine small intestine and fertilization takes place under low oxygen tensions. The unembryonated egg that leaves the host is metabolically quiescent, has no detectable cytochrome oxidase activity or ubiquinone and appears to be transcriptionally inactive (Cleavinger et al., 1989 Takamiya et al., 1993). Embryonation requires oxygen and after about 48-72 h is accompanied by... 

Komuniecki, R. and Komuniecki, P.R. (1995) Aerobic-anaerobic transitions in energy metabolism during the development of the parasitic nematode Ascaris suum. In Boothroyd, J.C. and Komuniecki, R. (eds) Molecular Approaches to Parasitolog. Wiley-Liss, New York, pp. 109-121. 

Tielens, A.G. and Roos, M.H. (1994) Differential expression of two succinate dehydrogenase subunit-(3 genes and a transition in energy metabolism during the development of the parasitic nematode Haemonchus contortus. Molecular and Biochemical Parasitology 66, 273-281. 

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. 

Kubiak, T.M., Maule, A.G., Marks, N.J., Martin, R.A. and Weist, J.R. (1996) Importance of the proline residue to the functional activity and metabolic stability of the nematode FMRFamide-related peptide, KPNFIRFamide (PF4). Peptides 17, 1267-1277. 

Depuration rates of diazinon differed significantly for two species of nematodes, Panagrellus redivivus and Bursaphelenchus xylophilus (Al-Attar and Knowles 1982). Both species showed maximum uptake of radiolabeled diazinon between 6 and 12 h, and both metabolized diazinon to diazoxon and pyrimidinol. By 96 h, 95% of the diazinon in P. redivivus had been metabolized, but only 26% was transformed in B. xylophilus, again demonstrating variability in diazinon metabolism between related species. 

Al-Attar, H.J. and C.O. Knowles. 1982. Diazinon uptake, metabolism, and elimination by nematodes. Arch. Environ. Contam. Toxicol. 11 669-673. 

Thiabendazole (Mintezol) inhibits fumarate reductase and electron transport-associated phosphorylation in helminths. Interference with ATP generation decreases glucose uptake and affects the energy available for metabolism. Benzimidazole anthelmintics as a class (e.g., thiabendazole, mebendazole, and albendazole), bind selectively to (3-tubulin of nematodes (roundworms), ces-todes (tapeworms), and trematodes (flukes). This inhibits microtubule assembly, which is important in a number of helminth cellular processes, such as mitosis, transport, and motihty. 

Febantel is a prodrug anthelminthic metabolized in vivo to fenbendazole and thereafter to oxfendazole. It is administered to cattle, sheep, and swine for treatment and control of gastrointestinal nematodes at dosages of 5-7.5 mg/kg bw. Fenbendazole, although not teratogenic per se, gives rise to the teratogenic oxfendazole. 

Trichlorphon is a precursor of dichlorvos used in swine and horses against gastrointestinal nematodes at dosages of 40-50 mg/kg bw. It is metabolized rapidly to dichlorvos, which is responsible for its therapeutic efficacy. The toxicity of trichlorphon is similar to that of dichlorvos. 

In 1966 the second modern broad spectrum anthelmintic, tetramisole (9), was introduced by Jannsen. The discovery of this drug followed the observation that the thiazothienol (10) was metabolized to an active compound in chickens. This was shown to be the thiazothielite (11) which led ultimately to the discovery of tetramisole (9). Later investigations showed that most of the activity of tetramisole (9) was due to the L-isomer, levamisole, which was more potent and less toxic than the D-isomer. Since their introduction, tetramisole (9) and levamisole have probably become the most widely used anthelmintics against a broad range of nematodes in pigs, sheep and poultry. Furthermore, unlike most benzimidazole carbamates, which are rather insoluble and must be given as an oral drench, levamisole may be given by the more convenient injectable route at a dose of 7.5 mg kg-1. 

Parasitic stages, on the other hand, generally do not use oxygen as the final electron acceptor but use fermentative processes to obtain most of their ATP. For these stages, an uneconomical energy metabolism is not detrimental, as the host provides the nutrients. Most adult flatworms inside the final host produce end products of a fermentative carbohydrate breakdown, such as succinate, acetate, propionate and lactate. These end products are formed via malate dismutation, a fermentative pathway, which is present in all types of parasitic worms (flatworms as well as many nematodes), but which is also present in animals like freshwater snails, mussels, oysters and other marine organisms. Malate dismutation is linked to a specially... 

Diaz, F. and Komuniecki, R.W. (1994) Pyruvate dehydrogenase complexes from the equine nematode, Parascaris equorum, and the canine cestode, Dipylidium caninum, helminths exhibiting anaerobic mitochondrial metabolism. Molecular and Biochemical Parasitology 67, 289-299. 

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