The metabolism of carbohydrate by pleomorphic African trypanosomes

Flynn, I.W.; Bowman, I.B.R.

doi:10.1016/0305-0491(73)90281-2

Cited by 34 publications

(25 citation statements)

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“…In contrast, long slender fosms lysed in the absence of either glucose or glycerol as substrate. Furthermore, oxygen consumption was stimulated in water-lysed preparations of transitional (but not long slender) forms by 2-oxoglutarate with either ADP or GDP; this respiration was sensitive to rotenone (Flynn and Bowman, 1973). The conclusion was that transitional forms contain an active decarboxylase system for a-oxoacid catabolism but the corollary of mitochondrial ATP production was not suggested.…”

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“…However, earlier work by Vickerman (1965) and Flynn and Bowman (1973) showed that populations with significant numbers of transitional bloodstream forms were able to maintain cell motility and oxygen utilization in the presence of 2-oxoglutarate, a Krebs cycle intermediate. In contrast, long slender fosms lysed in the absence of either glucose or glycerol as substrate.…”

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Non‐cytochrome mediated mitochondrial ATP production in bloodstream form Trypanosoma brucei brucei

Ej¹,

Rk²,

Pollakis³

et al. 1993

European Journal of Biochemistry

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The life cycle of Trypanosoma brucei brucei involves a series of differentiation steps characterized by marked changes in mitochondrial development and function. The bloodstream forms of this parasite completely lack cytochromes and have not been considered to have any Krebs cycle function. It has been suggested that glycolysis is the sole source of ATP in all bloodstream forms. However, earlier results indicated that in the mitochondria of the transitional intermediate/short stumpy bloodstream forms, the biochemical pathways are present that could allow intra-mitochondrial production of ATP. Using a high mannitol buffer to enhance permeability, we confirm previous observations showing that transitional forms maintain motility and respiratory activity with 2-oxoglutarate as the sole substrate. Using a luminometer to measure intracellular ATP levels via the luciferinlluciferase chemiluminescence assay, we show that these same transitional forms, but not long slender forms, maintain high levels of intracellular ATP in the presence of 2-oxoglutarate. Further, in the presence of bongkrekic acid, an inhibitor of the mitochondrial adenine nucleotide translocase, ATP levels are reduced with subsequent death and lysis of the cells when 2-oxoglutarate, but not glucose, is used as sole substrate. These data are direct evidence of ATP production by transitional bloodstream form mitochondria.Trypanosoma brucei brucei is of medical and economic importance as the agent of human African sleeping sickness and nagana in cattle. The life cycle of the parasite in the mammalian host begins with metacyclic forms injected with the bite of the tsetse fly vector. These metacyclics subsequently transform into the rapidly dividing long slender forms which in turn give rise to intermediate and short stumpy forms, stages suggested to be pre-adapted to survive in the vector if ingested with a blood meal. In this report we refer to the intermediate and short stumpy bloodstream forms as transitional bloodstream forms. Several aspects of the metabolism of bloodstream 7: brucei brucei are known to be unique and have been identified as targets for chemotherapy (Fairlamb, 1989;Clarkson and Brohn, 1976). Of special interest is the mitochondrion which undergoes marked differentiation and development as the organism progresses through its life cycle (Vickerman, 1965). The procyclic or insect midgut form has cytochromes and Krebs cycle function whereas these are both reported to be absent in bloodstream form mitochondria which have high respiratory activity but a limited range of function (for review see Fairlamb and Opperdoes, 1976).Glycolysis is generally considered the sole source of ATP in all bloodstream forms. However, earlier work by Vickerman (1965) and Flynn and Bowman (1973) showed that populations with significant numbers of transitional bloodstream forms were able to maintain cell motility and oxygen utilization in the presence of 2-oxoglutarate, a Krebs cycle intermediate. In contrast, long slender fosms lysed in the absence of Correspo...

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Non‐cytochrome mediated mitochondrial ATP production in bloodstream form Trypanosoma brucei brucei

Ej¹,

Rk²,

Pollakis³

et al. 1993

European Journal of Biochemistry

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“…During this life cycle, trypanosomes encounter different environments to which they have adapted, resulting in distinct stages, characterized by morphological as well as metabolic changes. Long slender BSF trypanosomes degrade glucose by glycolysis and excrete pyruvate as the sole metabolic end product (12,13,23). On the other hand, PCF trypanosomes do not excrete pyruvate but degrade glucose to acetate and succinate as main end products (25).…”

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“…On the other hand, PCF trypanosomes do not excrete pyruvate but degrade glucose to acetate and succinate as main end products (25). Krebs cycle activity was thought previously to be present in trypanosomatids, at least in insect stages of some African trypanosomatids (3,9,10,12,21). However, this presumed flux through the Krebs cycle is supported only poorly by direct experimental evidence and was based mainly on the presence of certain enzyme activities.…”

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Adaptations in the Glucose Metabolism of Procyclic Trypanosoma brucei Isolates from Tsetse Flies and during Differentiation of Bloodstream Forms

et al. 2009

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“…Bloodstream forms of the parasite depend exclusively on substrate-level phosphorylation for ATP production through glycolysis, which proceeds as far as pyruvate (Flynn and Bowman, 1973) (Fig. 1).…”

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confidence: 99%

The silicon trypanosome

et al. 2010

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S U M M A R YAfrican trypanosomes have emerged as promising unicellular model organisms for the next generation of systems biology. They offer unique advantages, due to their relative simplicity, the availability of all standard genomics techniques and a long history of quantitative research. Reproducible cultivation methods exist for morphologically and physiologically distinct life-cycle stages. The genome has been sequenced, and microarrays, RNA-interference and high-accuracy metabolomics are available. Furthermore, the availability of extensive kinetic data on all glycolytic enzymes has led to the early development of a complete, experiment-based dynamic model of an important biochemical pathway. Here we describe the achievements of trypanosome systems biology so far and outline the necessary steps towards the ambitious aim of creating a ' Silicon Trypanosome ', a comprehensive, experiment-based, multi-scale mathematical model of trypanosome physiology. We expect that, in the long run, the quantitative modelling enabled by the Silicon Trypanosome will play a key role in selecting the most suitable targets for developing new anti-parasite drugs.

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The metabolism of carbohydrate by pleomorphic African trypanosomes

Cited by 34 publications

References 20 publications

Non‐cytochrome mediated mitochondrial ATP production in bloodstream form Trypanosoma brucei brucei

Non‐cytochrome mediated mitochondrial ATP production in bloodstream form Trypanosoma brucei brucei

Adaptations in the Glucose Metabolism of Procyclic Trypanosoma brucei Isolates from Tsetse Flies and during Differentiation of Bloodstream Forms

The silicon trypanosome

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