Oxidation of Leucine by Leishmania donovani

Blum, J. J.

doi:10.1111/j.1550-7408.1991.tb06075.x

Cited by 15 publications

(12 citation statements)

References 26 publications

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“…Leishmania species, and to a minor extent T. cruzi , can synthesize sterols starting from Leu (Ginger et al ., 2000). Intact promastigote Leishmania donovani have been shown to decarboxylate Leu and ketocapronate, its deamination product, suggesting that BCAA catabolism takes place in the parasites (Blum, 1991). The second step in the degradation of Ile, Val and Leu is the oxidative decarboxylation of the corresponding 2‐keto acid to the respective acyl‐CoA.…”

Section: Discussionmentioning

confidence: 99%

Lipoamide dehydrogenase is essential for both bloodstream and procyclic Trypanosoma brucei

Roldán

Comini

Crispo

et al. 2011

Molecular Microbiology

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SummaryLipoamide dehydrogenase (LipDH) is a component of four mitochondrial multienzyme complexes. RNA interference or the deletion of both alleles in bloodstream Trypanosoma brucei resulted in an absolute requirement for exogenous thymidine. In the absence of thymidine, lipdh-/-parasites showed a severely altered morphology and cell cycle distribution. Most probably, in bloodstream cells with their only rudimentary mitochondrion, LipDH is required as component of the glycine cleavage complex which generates methylene-tetrahydrofolate for dTMP and thus DNA synthesis. The essential role of LipDH in bloodstream parasites was confirmed by an in vivo model. Lipdh-/-cells were unable to infect mice. Our data further revealed that degradation of branched-chain amino acids takes place but is dispensable. In cultured bloodstream -but not procyclic -African trypanosomes, the total cellular concentration of LipDH increases with increasing cell densities. In procyclic parasites, LipDH mRNA depletion caused an even stronger proliferation defect that was not reversed by thymidine suggesting that in the fully elaborated mitochondrion of these cells the primary effect is not on the glycine cleavage complex. Since the medium used for the cultivation of procyclic cells was not supplemented with glucose, impairment of the 2-ketoglutarate dehydrogenase complex is probably the main effect of LipDH depletion.

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Section: Discussionmentioning

confidence: 99%

Lipoamide dehydrogenase is essential for both bloodstream and procyclic Trypanosoma brucei

Roldán

Comini

Crispo

et al. 2011

Molecular Microbiology

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“…In response to a decrease in medium osmolality, the cells undergo a rapid decrease in length and a rapid release of alanine and other ninhydrinpositive compounds [5]. In response to an increase in medium osmolality, the rates of oxidation of alanine, glutamate, laurate, leucine, and glucose are inhibited [2,3]. The present study shows that hyperosmolality not only inhibits a number of oxidative pathways, but also inhibits a biosynthetic pathway, the glyoxylate cycle and/or the pathway leading from glucose-6-phosphate to mannan.…”

Section: Resultsmentioning

confidence: 99%

Incorporation of Label from Acetate and Laurate into the Mannan of Leishmania donovani via the Glyoxylate Cycle

Keegan

Blum

1993

J Eukaryotic Microbiology

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Leishmania donovani promastigotes in late-stationary phase incorporated label from [2-14C]acetate and [1-14C]laurate into the mannose residues of mannan, thus confirming the presence of a functional glyoxylate bypass in these parasitic protozoa. Isolated, washed calls also incorporated label from [2-14C]acetate and [1-14C]laurate into mannan during a 1-hr incubation in buffer. Glucose had no effect on label incorporation into mannan, but glutamate caused over a four-fold increase in incorporation from [2-14C]acetate and a 2.4-fold increase from [1-14C]laurate. Staurosporine, a protein kinase inhibitor that inhibits glutamate and alanine oxidation, did not inhibit label incorporation from [2-14C]acetate into mannan. Hyperosmolality caused about a 33% inhibition of label incorporation into mannan. These results show the glyoxylate cycle and/or the subsequent biosynthetic pathway from fructose-6-phosphate to mannan are subject to regulation.

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“…It has been shown that leucine oxidation by L. donovani promastigotes is inhibited by glucose and by alanine, but not by glutamate [4]. It was of interest, therefore, to begin this study of arginine catabolism by ascertaining whether the rate of urea formation was affected by glucose or by alanine.…”

Section: Resultsmentioning

confidence: 99%

“…Three milliliters of a stock culture were inoculated into 50 ml of medium in a 500-ml capacity Erlenmeyer flask and grown for 48 h at 26" C under air. An additional 50 ml of medium was then added and the flasks transferred to a shaker bath (80 strokedmin) maintained at 26" C for about 17 h (late log phase) 4 1 h, 65 h, or 89 h (1 -day, 2-day, or 3-day stationary phase, respectively). The cultures were then centrifuged for 4 min at 1,400 g at room temperature, resuspended in Hanks' Balanced Salt Solution excluding glucose or phenol red (HBSS-), washed twice, and resuspended in a suitable volume of HBSS-.…”

Section: Methodsmentioning

confidence: 99%

“…The results obtained from these studies are discussed in terms of the effects of metabolites of glucose and 2-deoxyglucose on urea formation and the effects of the amino acids themselves on arginine transport into cells. Since earlier studies had shown interesting effects of osmotic conditions on cell shape [ l l , 121 and metabolism [3,4,6, 261 the effects of osmotic conditions on arginine catabolism were also examined.…”

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Arginine Catabolism by Leishmania donovani Promastigotes

Blum¹

1992

The Journal of Protozoology

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Leishmania donovani promastigotes were grown to late log phase, washed and resuspended in iso-osmotic buffer containing L-arginine, and the rate of urea formation was then measured under various conditions. Addition of glucose or mannose activated urea formation, whereas 2-deoxyglucose inhibited and 6-deoxyglucose had no effect. Addition of alanine or of alpha-aminoisobutyrate inhibited urea formation, alanine causing a greater inhibition than alpha-aminoisobutyrate. Addition of leucine, proline, glycine, or lysine had no effect on urea formation. The presence of glutamate also increased the rate of urea formation from arginine, but to a lesser extent than did glucose. The presence of both glucose and alanine caused no net change in urea formation, whereas the inhibitory effect of alanine exceeded the activating effect of glutamate, so that a small inhibition in the rate of urea formation occurred in the presence of both alanine and glutamate. Cells grown to 3-day stationary phase had a markedly reduced rate of arginine catabolism to urea, but the activating effect of glucose and the inhibitory effect of alanine were qualitatively similar to their effects on late log phase cells. Addition of water to cells suspended in buffer also inhibited urea formation, but this appeared to be due primarily to the release of alanine caused by the hypo-osmotic stress. Addition of mannitol to cells suspended in buffer caused a small inhibition of arginine catabolism. Addition of dibutyrylcyclic AMP, 3',5'-cyclic GMP, phorbol myristic acid, or A23187 had no effect on the rate of urea formation from arginine.(ABSTRACT TRUNCATED AT 250 WORDS)

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Oxidation of Leucine by Leishmania donovani

Cited by 15 publications

References 26 publications

Lipoamide dehydrogenase is essential for both bloodstream and procyclic Trypanosoma brucei

Lipoamide dehydrogenase is essential for both bloodstream and procyclic Trypanosoma brucei

Incorporation of Label from Acetate and Laurate into the Mannan of Leishmania donovani via the Glyoxylate Cycle

Arginine Catabolism by Leishmania donovani Promastigotes

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