Energy metabolism fumarate reductase

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. 

Fig. 5.4. Two types of energy metabolism in cestodes. (a) Type 1 homolactate fermentation, (b) Type 2 Malate dismutation. Reaction 3 involves a carboxylation step decarboxylation occurs at 6, 7 and 10. Reducing equivalents are generated at reactions 6 and 7 one reducing equivalent is used at reaction 9. Thus, when the mitochondrial compartment is in redox balance and malate is the sole substrate, twice as much propionate as acetate is produced. Key 1, pyruvate kinase 2, lactate dehydrogenase 3, phosphoenolpyruvate carboxykinase 4, malate dehydrogenase 5, mitochondrial membrane 6 malic enzyme 7, pyruvate dehydrogenase complex 8, fumarase 9, fumarate reductase 10, succinate decarboxylase complex. indicates reactions at which ATP is synthesised from ADP cyt, cytosol mit, mitochondrion. (After Bryant Flockhart, 1986.)...

Fumarate-reductase, which converts fumarate into succinate in mitochondria, plays an important role in the anaerobic glucose metabolism and eventual energy production in many helminths. Thus, inhibition of this enzyme was considered to... 

Fates of tyrosine. Tyrosine can be degraded by oxidative processes to ace-toacetate and fumarate which enter the energy generating pathways of the citric acid cycle to produce ATP as indicated in Figure 38-2. Tyrosine can be further metabolized to produce various neurotransmitters such as dopamine, epinephrine, and norepinephrine. Hydroxylation of tyrosine by tyrosine hydroxylase produces dihydroxyphenylalanine (DORA). This enzyme, like phenylalanine hydroxylase, requires molecular oxygen and telrahydrobiopterin. As is the case for phenylalanine hydroxylase, the tyrosine hydroxylase reaction is sensitive to perturbations in dihydropteridine reductase or the biopterin synthesis pathway, anyone of which could lead to interruption of tyrosine hydroxylation, an increase in tyrosine levels, and an increase in transamination of tyrosine to form its cognate a-keto acid, para-hydroxyphenylpyruvate, which also would appear in urine as a contributor to phenylketonuria. 

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