Transhydrogenase activities and malate dismutation linked to fumarate reductase system in the filarial parasite Setaria digitata.
Setaria digitata, a cattle filarial parasite, similar to human filarial parasites, possesses significant activities of the 4 transhydrogenases namely NADH-NAD+, NADPH-NAD+, NADH-NADP+, and NADPH-NADP+ in the sonicated mitochondria like particles. The transhydrogenases appear to regulate the metabolic pathways of the parasite in response to the presence of adenyl nucleotides and are non-energy linked. Observations on the transhydrogenase and fumarate reductase activities show the existence of a protein bound NAD in the MLP and a linkage between the fumarate reductase system and malic enzyme through transhydrogenases. The malate dismutation reaction is the result of malic and fumarase enzyme activities. Fumarase and fumarate reductase activities result in succinate formation under anaerobic conditions showing major energy production at the fumarate reductase site. The existence of acetate kinase, phosphotransacetylase, pyruvate carboxylase, propionyl CoA carboxylase and CoA transferase enzymes in the mitochondrial system shows the presence of other energy producing sites in the parasite. The transhydrogenase system, NAD+/NADP+ malic enzyme, fumarase and fumarate reductase are the key enzymes of, production of reducing power for synthetic reactions and regulation of oxidative and reductive stages of the mitochondrial system. Hence, specific drugs targeted against this interconnected complex enzyme system, will be very effective in the control of filarial parasites.
Unnikrishnan
L S
LS
Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram, India.
Raj
R K
RK
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002417:Cattle; D004734:Energy Metabolism; D005649:Fumarate Hydratase / Q000378:metabolism; D006801:Humans; D008291:Malate Dehydrogenase / Q000378:metabolism; D008293:Malates / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D009250:NADP Transhydrogenases / Q000378:metabolism*; D017182:Setaria Nematode / Q000201:enzymology / Q000378:metabolism*; D013385:Succinate Dehydrogenase / Q000378:metabolism*
D008293:Malates; D009243:NAD; D009249:NADP; C030298:malic acid; D000255:Adenosine Triphosphate; D008291:Malate Dehydrogenase; C030574:malate dehydrogenase (decarboxylating); D013385:Succinate Dehydrogenase; D009250:NADP Transhydrogenases; D005649:Fumarate Hydratase