Abstract
Malate dehydrogenase (MDH) (E.C.1.1.1.37) activity was detected in the filariaMolinema dessetae at a level similar to those found in other filariae. InM. dessetae, the cytoplasmic form (c-MDH) predominated and the study was performed on partially purified fractions. The pH optimum for oxaloacetate reduction was 6.1, with maximal activity at 7811 nmol min−1 mg protein−1, but high concentrations of oxaloacetate inhibited MDH activity. TheK m value for oxaloacetate was determined as 22 μM forM. dessetae c-MDH and 33μM for mammalian c-MDH. Anthelmintic drugs were compared as potential inhibitors of filarial and mammalian c-MDH. Among the compounds evaluated, amocarzine showed a specific inhibitory effect on filarial c-MDH through only at high concentrations. Suramin alone showed an inhibitory effect at low concentrations (K i=1.15 μM) but without selective action towards filarial c-MDH. The suramin type of inhibition was found to be competitive. Suramin probably acts on both enzymes in the same manner. Nevertheless,M. dessetae c-MDH is proposed as a suitable enzyme assay model to screen MDH inhibitors as potential filaricides.
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References
Anwar N, Ansari AA, Ghatak S, Krishna Murti CR (1977)Setaria cervi: enzymes of glycolysis and PEP-succinate pathway. Z. Parasitenkd 51:275–283
Barrett J, Beis I (1973) The redox state of the free nicotinamide adenine dinucleotide couple in the cytoplasm and the mitochondria of muscle tissue fromAscaris lumbricoides (Nematoda). Comp Biochem Physiol [A] 44:331–340
Barrett J, Mendis AHW, Butterworth PE (1986) Carbohydrate metabolism ofBrugia pahangi. Int J Parasitol 16:465–469
De Zoeten LW, Posthuma D, Tipker J (1969) Intermediary metabolism of the liver flukeF. hepatica. I. Biosynthesis of propionic acid. Hoppe Seylers Z Physiol Chem 350:683–690
Dixon M (1979) Enzyme inhibition and activation. A. Inhibitors. In: Dixon M, Webb EC (eds) Enzymes, chap 8, 3rd edn. Longman Group Ltd, pp 350
Dubinsky P, Rybos M (1981) Activity of malate dehydrogenase in the reproductive organs and muscles ofAscaris suum. Helminthologia 18:205–213
Fioravanti CF (1982) Mitochondrial malate dehydrogenase, decarboxylating (“malic enzyme”) and transhydrogenase activities of adultH. microstoma. J Parasitol 68:213–220
Gayral P, Bories C, Loiseau P, Gueyouche C (1987)Molinema dessetae forin vitro andin vivo filaricidal evaluation. Trop Med Parasitol 38:65
Hussain H, Shukla OP, Ghatak S, Kaushal NA (1990) Enzymes of PEP succinate pathway inSetaria cervi and effect of anthelmintic drugs. Ind J Exp Biol 28:871–875
Lineweaver H, Burk D (1934) The determination of enzyme dissociation constants. J Am Chem Soc 56:658–666
Loiseau PM, Gayral P, Petek F (1993) Purification and properties of phosphoenolpyruvate carboxylase fromMolinema dessetae (Nematoda: Filarioidea): Parasitology 106:55–61
Moon TW, Hulbert WC, Mustapha T, Mettrick DF (1977) A study of lactate dehydrogenase and malate dehydrogenase in adultHymenolepis diminuta (Cestoda). Comp Biochem Physiol [B] 56:249–254
Pennoit de Cooman E, van Grembergen G (1942) Vergelijkend Onderzock van het Fermenten-system bij vrijlevende en parasitaire Plathelminthen. Ver voorstel K. Ulaa Acad Wetensch 4:7–77
Prichard RK, Schofield PJ (1968) A comparative study of the TCA cycle enzymes inF. hepatica and rat liver. Comp Biochem Physiol 25:1005–1019
Ramp T, Köhler P (1984) Glucose and pyruvate catabolism inLitomosoides carinii. Parasitology 89:229–244
Rhodes MB, Ferguson DL, Marsh CL (1970)Haemonchus contortus: Enzymes. I. Isoelectric focusing of malate dehydrogenase in sucrose and polyacrylamide gels. Exp Parasitol 28:194–209
Sanchez-Moreno M, Salas-Peregrin JM, Leon P, Garcia-Ruiz MA, Lemaur M, Monteoliva M (1987) Malate dehydrogenases in helminth parasites. Inhibitions by benzimidazoles and pyrimidine derivatives. Drug Res 37:1327–1331
Sedmak JJ, Grossberg SE (1977) A rapid, sensitive and versatile assay for protein using Coomassie brillant blue G 250. Anal Biochem 79:544–552
Shonk CE, Boxer GE (1964) Enzyme patterns in human tissues. I. Methods for the determination of glycolytic enzyme. Cancer Res 24:709–721
Srivastava VML, Chatterjee RK, Sen AB, Ghatak S, Krishna Murti CR (1970) Glycolysis inLitomosoides carinii, the filarial parasite of the cotton rat. Exp Parasitol 28:176–185
Srivastava VML, Ghatak S (1971) Glycolytic and carbon dioxide metabolizing enzymes inChandlerella hawkingi. Ind J Biochem Biophys 8:108–111
Walter RD (1979) Inhibition of lactate dehydrogenase activity fromDirofilaria immitis by suramin. Tropenmed Parasitol 30:463–465
Walter RD, Schulz-Key H (1980)Onchocerca volvulus: effect of suramin on lactate dehydrogenase and malate dehydrogenase. Tropenmed Parasitol 31:55–58
Zee DS, Zinkham WH (1968) Malate dehydrogenase inAscaris suum: characterization, ontogeny and genetic control. Arch Biochem Biophys 126:574–584
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Loiseau, P.M., Maarouf, M., Gayral, P. et al. Comparative effects of anthelmintics on c-MDH fromMolinema dessetae (Nematoda: Filarioidea) and from a mammal. Parasitol Res 79, 397–401 (1993). https://doi.org/10.1007/BF00931829
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DOI: https://doi.org/10.1007/BF00931829