Parasite enzymes as potential targets for antiparasitic chemotherapy. 1984

C C Wang

I have thus far listed a total of 10 potential targets for antiparasitic chemotherapeutic consideration. This is by no means a completed list. Many more will be added to it with time and with more future findings. Among these 10 targets (summarized in Table I), however, one may gain some insight and see a few interesting general trends: (1) Nucleic acid metabolism and carbohydrate-energy metabolism in protozoan parasites appear to be targets for fruitful chemotherapeutic attacks. Their being useful targets results generally from the deficient metabolism in the protozoan parasites. Thus, the main vulnerability among the protozoan parasites is closely associated with their parasitic nature. (2) Microtubules and nervous systems appear to be the main chemotherapeutic targets in helminths. They differ from those in the host not because of their parasitic nature but, more likely, because of the evolutionary distance separating the mammalian hosts and the primitive metazoa. Thus, free-living nematodes, such as Caenorhabditis elegans, have their microtubules just as susceptible to the benzimidazole anthelmintics as those from the parasitic worms. The motoneuronal map of C. elegans is identical with that of Ascaris lumbricoides. Both worms are similarly immobilized by levamisole, piperazine, avermectins, etc. The dual insecticidal and antiexoparasite activities found in the avermectins and milbemycins may also suggest that the free-living insects and the ticks and lice may have the same GABA nervous system. This main discrepancy between protozoan parasites and metazoan parasites may be partly attributable to the higher mutation rates and higher frequencies of genetic recombination among the protozoa, evidenced by the higher rates of development of drug resistance among them. The fast adaptation to a new environment may be essential for survival, but it would also lead to metabolic deficiencies after the protozoa lived in a luxurious environment for a while. This revelation may suggest that future chemotherapeutic studies on parasitic helminths can utilize free-living helminths as models to eliminate many unnecessary technical difficulties. Also, there perhaps could be a further classification among the parasites to term the protozoa "true parasites" and the helminth "pseudo-parasites" from the viewpoint of chemotherapy.

UI MeSH Term Description Entries
D007658 Ketone Oxidoreductases Oxidoreductases that are specific for KETONES. Oxidoreductases, Ketone
D008928 Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed) Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D009420 Nervous System The entire nerve apparatus, composed of a central part, the brain and spinal cord, and a peripheral part, the cranial and spinal nerves, autonomic ganglia, and plexuses. (Stedman, 26th ed) Nervous Systems,System, Nervous,Systems, Nervous
D010271 Parasites Invertebrate organisms that live on or in another organism (the host), and benefit at the expense of the other. Traditionally excluded from definition of parasites are pathogenic BACTERIA; FUNGI; VIRUSES; and PLANTS; though they may live parasitically. Parasite
D010272 Parasitic Diseases Infections or infestations with PARASITES. They are often contracted through contact with an intermediate vector, but may occur as the result of direct exposure. Parasite Infections,Parasitic Infections,Disease, Parasitic,Diseases, Parasitic,Infection, Parasite,Infection, Parasitic,Infections, Parasite,Infections, Parasitic,Parasite Infection,Parasitic Disease,Parasitic Infection
D010430 Pentosyltransferases Enzymes of the transferase class that catalyze the transfer of a pentose group from one compound to another.
D010770 Phosphotransferases A rather large group of enzymes comprising not only those transferring phosphate but also diphosphate, nucleotidyl residues, and others. These have also been subdivided according to the acceptor group. (From Enzyme Nomenclature, 1992) EC 2.7. Kinases,Phosphotransferase,Phosphotransferases, ATP,Transphosphorylase,Transphosphorylases,Kinase,ATP Phosphotransferases
D011622 Pterins Compounds based on 2-amino-4-hydroxypteridine. Pterin
D004579 Electron Transport The process by which ELECTRONS are transported from a reduced substrate to molecular OXYGEN. (From Bennington, Saunders Dictionary and Encyclopedia of Laboratory Medicine and Technology, 1984, p270) Respiratory Chain,Chain, Respiratory,Chains, Respiratory,Respiratory Chains,Transport, Electron
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme

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