The metabolism of <i>Leishmania donovani</i> in culture

The metabolism of [1-14C]- and [6-14C]glucose, [1-14C]ribose, [1-14C]- and [U-14C]alanine, and [1-14C]- and [5-14C]glutamate by the promastigotes of Leishmania braziliensis panamensis was investigated in cells resuspended in Hanks' balanced salt solution supplemented with ribose, alanine, or glutamate. The ratio of 14CO2 produced from [1-14C]glucose to that from [6-14C]glucose ranged from about two to six, indicating appreciable carbon flow through the pentose phosphate pathway. A functional pentose phosphate pathway was further demonstrated by the production of 14CO2 from [1-14C]ribose although the rate of ribose oxidation was much lower than the rate of glucose oxidation. The rate of 14CO2 production from [1-14C]glucose was almost linear with time of incubation, whereas that of [6-14C]glucose accelerated, consistent with an increasing rate of flux through the Embden-Meyerhof pathway during incubation. Increasing the assay temperature from 26 degrees C to 34 degrees C had no appreciable effect on the rates or time courses of oxidation of either [1-14C]- or [6-14C]glucose or of [1-14C]ribose. Both alanine and glutamate were oxidized by L. b. panamensis, and at rates comparable to or appreciably greater than the rate of oxidation of glucose. The ratios of 14CO2 produced from [1-14C]- to [U-14C]alanine and from [1-14C]- to [5-14C]glutamate indicated that these compounds were metabolized via a functioning tricarboxylic acid cycle and that most of the label that entered the tricarboxylic acid cycle was oxidized to carbon dioxide.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…It was noted above that glutamate is oxidized at an appreciable rate by L. 6. panamensis promastigotes.…”

Section: -I4c]-and [U-l4c]alanine On the Same Cells And Subtracting mentioning

confidence: 89%

Oxidation of Glucose, Ribose, Alanine, and Glutamate by Leishmania braziliensis panamensis1

Keegan

Sansone

Blum

1987

The Journal of Protozoology

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“…Metabolic studies done on both phases of these organisms have indicated that they are biochemically similar, although the oxygen consumption of the leptomonad (culture) form is greater. This difference is probably a quantitative rather than a qualitative phenomenon (3,8,15). Detailed studies on the biosynthesis of pyrimidines in both morphological forms are lacking, but the assumption that it too will be similar is not unreasonable.…”

Section: Discussionmentioning

confidence: 99%

Antileishmanial Effect of Allopurinol

Pfaller

Marr

1974

Antimicrob Agents Chemother

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Allopurinol (4-hydroxypyrazolo[3,4-d]pyrimidine) has been shown to inhibit the growth of Leishmania braziliensis in vitro at concentrations which are attainable in human tissues and body fluids. This compound is believed to act by interdicting the de novo synthesis of pyrimidines, probably through the formation of allopurinol ribotide. Its lack of toxicity makes it a potential candidate for animal experimentation and it may serve as a prototype for other agents with similar mechanisms of action.

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“…L mastigotes in the gut of their sandfly vectors or as amastigotes in macrophages of their mammalian host. Studies of the metabolism of Leishmania promastigotes grown in culture have yielded important information about the preferential utilization of substrates and release of products [2,4,11,241, and have demonstrated differences in substrate utilization depending on growth-phase [ 18, 2 11 or degree of subpassage [ 1 11. Such studies, however, give little insight into the metabolic pathways by which these substrates are used or into the interactions between substrates.…”

mentioning

confidence: 99%

Metabolic Interactions Between Glucose, Glycerol, Alanine and Acetate in Leishmania braziliensis panamensis Promastigotes

Darling

Davis

London

et al. 1989

The Journal of Protozoology

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13C-nuclear magnetic resonance (NMR) spectroscopy was used to investigate the products of glycerol and acetate metabolism released by Leishmania braziliensis panamensis promastigotes and also to examine the interaction of each of these substrates with glucose or alanine. The NMR data were supplemented by measurements of the rates of oxygen consumption and substrate utilization, and of 14CO2 production from 14C-labeled substrate. Cells incubated with [2-13C]glycerol released acetate, succinate and D-lactate in addition to CO2. Cells incubated with acetate released only CO2. More succinate C-2/C-3 than C-1/C-4 was released from both [2-13C]glycerol and [2-13C]glucose, indicating that succinate was formed predominantly by CO2 fixation followed by reverse flux through part of the Krebs cycle. Some redistribution of the position of labeling was also seen in alanine and pyruvate, suggesting cycling through pyruvate/oxaloacetate/phosphoenolpyruvate. Cells incubated with combinations of 2 substrates consumed oxygen at the same rate as cells incubated with 1 or no substrate, even though the total substrate utilization had increased. When promastigotes were incubated with both glycerol and glucose, the rate of glucose consumption was unchanged but glycerol consumption decreased about 50%, and the rate of 14CO2 production from [1,(3)-14C]glycerol decreased about 60%. Alanine did not affect the rates of consumption of glucose or glycerol, but decreased 14CO2 production from these substrates by increasing flow of label into alanine. Although glucose decreased alanine consumption by 70%, it increased the rate of 14CO2 production from [U-14C]- and [l-14C]alanine by about 20%.(ABSTRACT TRUNCATED AT 250 WORDS)

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The metabolism of Leishmania donovani in culture

Cited by 31 publications

References 7 publications

Oxidation of Glucose, Ribose, Alanine, and Glutamate by Leishmania braziliensis panamensis1

Oxidation of Glucose, Ribose, Alanine, and Glutamate by Leishmania braziliensis panamensis1

Antileishmanial Effect of Allopurinol

Metabolic Interactions Between Glucose, Glycerol, Alanine and Acetate in Leishmania braziliensis panamensis Promastigotes

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