Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.1.1.1 (alcohol dehydrogenase)
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Tritrichomonas foetus mutants resistant to metronidazole lack the hydrogenosomal enzymes pyruvate: ferredoxin oxidoreductase and hydrogenase. Hydrogenosomes of these organisms did not oxidize pyruvate or produce ATP in its presence. Elimination of hydrogenosomal metabolism of pyruvate was compensated by an increased rate of glycolysis. The resistant mutants excreted no organic acids and H2 as metabolic end products. Glycolysis of the resistant T. foetus KV1-1MR-100 can be summarized as 1 mol glucose----2 mol ethanol + 2 mol CO2. The parent strain KV1, excreting H2, CO2 and acidic end products, converted about 10% of glucose to ethanol. Both strains produced ethanol from pyruvate through the action of two cytoplasmic enzymes: pyruvate decarboxylase and alcohol dehydrogenase. The specific activity of the former enzyme, catalyzing nonoxidative decarboxylation of pyruvate to acetaldehyde, was nearly seven times higher in the resistant than in the parent strain. Alcohol dehydrogenase reducing acetaldehyde to ethanol was specific to NADPH; it catalyzed the reverse reaction only slowly, and displayed similar activities in both resistant and sensitive trichomonads. Development of anaerobic metronidazole resistance in T. foetus depended on the loss of pyruvate:ferredoxin oxidoreductase as well as on the ability to increase alcoholic fermentation.
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PMID:Metabolic differences between metronidazole resistant and susceptible strains of Tritrichomonas foetus. 637 46

Tritrichomonas foetus was found to contain NADP-specific malic enzyme. The activity was present in the cytosolic fraction and was about 5-fold higher in extracts of a metronidazole-resistant strain (KV1-1MR-100) than of the parent strain (KVc1). Electrophoresis under non-denaturing conditions and activity staining indicated the existence of 3 isozymes termed I, II and III in order of increasing electrophoretic mobility. Isozymes I and II were much less active than isozyme III in the parent strain, whereas all three isozymes had comparable activities in the resistant strain. NADP-malic enzymes were purified from the cytosolic fraction of the resistant strain to apparent homogeneity and were identified by SDS-PAGE as polypeptides of 41.5 kDa (I), 40.5 kDa (III) and as a mixture of both in equal amounts (II). The molecular mass of the three holoenzymes was about 180 kDa, as determined by gel-filtration on Sephacryl S-300 HR, indicating a tetrameric structure. Isozyme III was also purified from parent strain and shown to consist of the 40.5-kDa polypeptide. Km values for malate were 0.31, 0.65 and 1.35 mM for isozyme I, II and III, respectively. From these results we conclude that T. foetus+, which is required for the formation of ethanol by alcohol dehydrogenase, an NADP-specific enzyme in this species. This is particularly important for the resistant strain, in which ethanol is the major end-product of glucose metabolism.
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PMID:Identification, purification and separation of different isozymes of NADP-specific malic enzyme from Tritrichomonas foetus. 843 16