S-Adenosylmethionine and transmethylation reactions in trichomonads

Thong, Kam-Wah; Coombs, Graham H.; Sanderson, Barbara E.

doi:10.1007/bf00578503

Cited by 12 publications

(5 citation statements)

References 17 publications

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“…For instance, exogenous methionine is rapidly catabolised. Moreover, the parasite uses methionine to produce S-adenosylmethionine (SAM) for methylation reactions (49) with the resulting S-adenosylhomocysteine (SAH) being hydrolysed by SAH hydrolase (50) to homocysteine, which is even more rapidly catabolised by MGL. This would provide sulphide for the biosynthesis of cysteine using CS.…”

Section: Discussionmentioning

confidence: 99%

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Cysteine Biosynthesis in Trichomonas vaginalis Involves Cysteine Synthase Utilizing O-Phosphoserine

Westrop

Goodall

Mottram

et al. 2006

Journal of Biological Chemistry

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Trichomonas vaginalis is an early divergent eukaryote with many unusual biochemical features. It is an anaerobic protozoan parasite of humans that is thought to rely heavily on cysteine as a major redox buffer, because it lacks glutathione. We report here that for synthesis of cysteine from sulfide, T. vaginalis relies upon cysteine synthase. The enzyme (TvCS1) can use either O-acetylserine or O-phosphoserine as substrates. The K m values of the enzyme for sulfide are very low (0.02 mM), suggesting that the enzyme may be a means of ensuring that sulfide in the parasite is maintained at a low level. T. vaginalis appears to lack serine acetyltransferase, the source of O-acetylserine in many cells, but has a functional 3-phosphoglycerate dehydrogenase and an O-phosphoserine aminotransferase that together result in the production of O-phosphoserine, suggesting that this is the physiological substrate. TvCS1 can also use thiosulfate as substrate. Overall, TvCS1 has substrate specificities similar to those reported for cysteine synthases of Aeropyrum pernix and Escherichia coli, and this is reflected by sequence similarities around the active site. We suggest that these enzymes are classified together as type B cysteine synthases, and we hypothesize that the use of O-phosphoserine is a common characteristic of these cysteine synthases. The level of cysteine synthase in T. vaginalis is regulated according to need, such that parasites growing in an environment rich in cysteine have low activity, whereas exposure to propargylglycine results in elevated cysteine synthase activity. Humans lack cysteine synthase; therefore, this parasite enzyme could be an exploitable drug target.

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Section: Discussionmentioning

confidence: 99%

“…See Table 1 for key to abbreviations. MGL, methionine γ-lyase; SAM-MT, S-adenosylmethione-dependent methyltransferase (49); SAHH, S-adenosylhomocysteine hydrolase (50).…”

Section: Figmentioning

confidence: 99%

Cysteine Biosynthesis in Trichomonas vaginalis Involves Cysteine Synthase Utilizing O-Phosphoserine

Westrop

Goodall

Mottram

et al. 2006

Journal of Biological Chemistry

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“…The reaction at 37°C was monitored continuously by detecting the formation of lead sulfide spectrophotometrically at 360 nm. The molar extinction coefficient was taken as 5205 cm Ϫ1 M Ϫ1 (32).…”

Section: Cultivation Of L Major and L Mexicana-promastigotes Of L mentioning

confidence: 99%

3-Mercaptopyruvate Sulfurtransferase of LeishmaniaContains an Unusual C-terminal Extension and Is Involved in Thioredoxin and Antioxidant Metabolism

Williams

Kelly

Mottram

et al. 2003

Journal of Biological Chemistry

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Cytosolic 3-mercaptopyruvate sulfurtransferases (EC 2.8.1.2) of Leishmania major and Leishmania mexicana have been cloned, expressed as active enzymes in Escherichia coli, and characterized. The leishmanial singlecopy genes predict a sulfurtransferase that is structurally peculiar in possessing a C-terminal domain of some 70 amino acids. Homologous genes of Trypanosoma cruzi and Trypanosoma brucei encode enzymes with a similar C-terminal domain, suggesting that this feature, not known in any other sulfurtransferase, is a characteristic of trypanosomatid parasites. Short truncations of the C-terminal domain resulted in misfolded inactive proteins, demonstrating that the domain plays some key role in facilitating correct folding of the enzymes. The leishmanial recombinant enzymes exhibited high activity toward 3-mercaptopyruvate and catalyzed the transfer of sulfane sulfur to cyanide to form thiocyanate. They also used thiosulfate as a substrate and reduced thioredoxin as the accepting nucleophile, the latter being oxidized. The enzymes were expressed in all life cycle stages, and the expression level was increased under peroxide or hypo-sulfur stress. The results are consistent with the enzymes having an involvement in the synthesis of sulfur amino acids per se or iron-sulfur centers of proteins and the parasite's management of oxidative stress.

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“…Additionally, iron acquisition is not enhanced by the presence of NADH, a nucleotide reported to provide electrons to ferrireductases [Low et al, 1986;Berczi and Faulk, 1992;Riedel et al, 1995]. In fact, trichomonads are able to produce reducing volatile agents such as H2S or methanethiol , which have been suggested to participate in oxygen detoxification [Thong et al, 1986]. It could be that trichomonads are able to take advantage of their reducing environment to take up iron from holo-TF (Fig.…”

Section: Iron Uptake From Transferrin In T Foetusmentioning

confidence: 99%