Competition of several enzymes for a common substrate: a possible model of cellular events

Siebert, Günther; Pfaender, Peter; Kesselring, Kurt

doi:10.1016/0065-2571(69)90015-6

Cited by 10 publications

(4 citation statements)

References 27 publications

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“…The competing kinases (HK and GK) catalyze the first step of their respective pathways and therefore control the utilization of their substrate (glucose and glycerol, respectively). The competition of certain enzymes for a common substrate, in particular at branching metabolic points, is a well-known process used to finely tune metabolic fluxes [29]. However, as far as we know, this is the first example of an almost complete repression of one enzymatic activity (HK) by the large excess of another one (GK) competing for the same substrate, as a mechanism to control nutrient utilization.…”

Section: Plos Biologymentioning

confidence: 99%

Glycerol suppresses glucose consumption in trypanosomes through metabolic contest

Allmann

Wargnies²,

Plazolles³

et al. 2021

PLoS Biol

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Microorganisms must make the right choice for nutrient consumption to adapt to their changing environment. As a consequence, bacteria and yeasts have developed regulatory mechanisms involving nutrient sensing and signaling, known as “catabolite repression,” allowing redirection of cell metabolism to maximize the consumption of an energy-efficient carbon source. Here, we report a new mechanism named “metabolic contest” for regulating the use of carbon sources without nutrient sensing and signaling. Trypanosoma brucei is a unicellular eukaryote transmitted by tsetse flies and causing human African trypanosomiasis, or sleeping sickness. We showed that, in contrast to most microorganisms, the insect stages of this parasite developed a preference for glycerol over glucose, with glucose consumption beginning after the depletion of glycerol present in the medium. This “metabolic contest” depends on the combination of 3 conditions: (i) the sequestration of both metabolic pathways in the same subcellular compartment, here in the peroxisomal-related organelles named glycosomes; (ii) the competition for the same substrate, here ATP, with the first enzymatic step of the glycerol and glucose metabolic pathways both being ATP-dependent (glycerol kinase and hexokinase, respectively); and (iii) an unbalanced activity between the competing enzymes, here the glycerol kinase activity being approximately 80-fold higher than the hexokinase activity. As predicted by our model, an approximately 50-fold down-regulation of the GK expression abolished the preference for glycerol over glucose, with glucose and glycerol being metabolized concomitantly. In theory, a metabolic contest could be found in any organism provided that the 3 conditions listed above are met.

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Section: Plos Biologymentioning

confidence: 99%

Glycerol suppresses glucose consumption in trypanosomes through metabolic contest

Allmann

Wargnies²,

Plazolles³

et al. 2021

PLoS Biol

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“…This simple treatment has been applied to the competition for PEP between pyruvate kinase and alkaline phosphatase in mammalian tissues (146). Al though alkaline phosphatase has a high affinity for PEP at neutral pH, the role of this enzyme in the metabolism of PEP is not clear.…”

Section: Variations In Substrate Concentrationsmentioning

confidence: 99%

The Central Role of Phosphoenolpyruvate in Plant Metabolism

Davies¹

1979

Annu. Rev. Plant. Physiol.

134

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“…The competing kinases (HK and GK) catalyze the first step of their respective pathway and therefore control the utilization of their substrate (glucose and glycerol assimilation, respectively). The competition of given enzymes for a common substrate, in particular at branching metabolic points, is a well-known process used to finely tune metabolic fluxes (Siebert et al, 1969). However, as far as we know, this is the first example of an almost complete repression of one enzymatic activity (HK) by the large excess of another one (GK) competing for the same substrate, as a mechanism to control nutrient utilization.…”

Section: Resultsmentioning

confidence: 99%

“Metabolic contest”, a new way to control carbon source preference

Allmann¹,

Wargnies²,

Cahoreau³

et al. 2019

Preprint

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SUMMARYMicroorganisms must make the right choice for nutrient consumption to adapt to their changing environment. As a consequence, bacteria and yeasts have developed regulatory mechanisms involving nutrient sensing and signaling, allowing to redirect cell metabolism to maximize the consumption of an energy-efficient carbon source. Here, we report a new mechanism, named “metabolic contest”, for regulating the use of carbon sources without nutrient sensing and signaling. In contrast to most microorganisms, trypanosomes show a glycerol-to-glucose preference that depends on the combination of three conditions: (i) the sequestration of both metabolic pathways in the same subcellular compartment, here in the peroxisomal-like organelles named glycosomes; (ii) the competition for the same substrate, here ATP, with the first enzymatic step of the glycerol and glucose metabolic pathways being both ATP-dependent (glycerol kinase and hexokinase, respectively) and (iii) an unbalanced activity between the competing enzymes, here the glycerol kinase activity being ~80-fold higher than the hexokinase activity.

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Competition of several enzymes for a common substrate: a possible model of cellular events

Cited by 10 publications

References 27 publications

Glycerol suppresses glucose consumption in trypanosomes through metabolic contest

Glycerol suppresses glucose consumption in trypanosomes through metabolic contest

The Central Role of Phosphoenolpyruvate in Plant Metabolism

“Metabolic contest”, a new way to control carbon source preference

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