dorsal/arxiv
View SchemaThe control of phenotype: connecting enzyme variation to physiology
| Authors | Homayoun Bagheri-Chaichian, Joachim Hermisson, Juozas R. Vaisnys, Gunter P. Wagner |
|---|---|
| Categories | |
| ArXiv ID | physics/0202026 |
| URL | https://arxiv.org/abs/physics/0202026 |
Abstract
Metabolic control analysis (Kacser & Burns (1973). Symp. Soc. Exp. Biol. 27, 65-104; Heinrich & Rapoport (1974). Eur. J. Biochem. 42, 89-95) was developed for the understanding of multi-enzyme networks. At the core of this approach is the flux summation theorem. This theorem implies that there is an invariant relationship between the control coefficients of enzymes in a pathway. One of the main conclusions that has been derived from the summation theorem is that phenotypic robustness to mutation (e.g. dominance) is an inherent property of metabolic systems and hence does not require an evolutionary explanation (Kacser & Burns (1981). Genetics. 97, 639-666; Porteous (1996). J. theor. Biol. 182, 223-232). Here we show that for mutations involving discrete changes (of any magnitude) in enzyme concentration the flux summation theorem does not hold. The scenarios we examine are two-enzyme pathways with a diffusion barrier, two enzyme pathways that allow for enzyme saturation and two enzyme pathways that have both saturable enzymes and a diffusion barrier. Our results are extendable to sequential pathways with any number of enzymes. The fact that the flux summation theorem cannot hold in sequential pathways casts serious doubts on the claim that robustness with respect to mutations is an inherent property of metabolic systems.
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"abstract": "Metabolic control analysis (Kacser \u0026 Burns (1973). Symp. Soc. Exp. Biol. 27,\n65-104; Heinrich \u0026 Rapoport (1974). Eur. J. Biochem. 42, 89-95) was developed\nfor the understanding of multi-enzyme networks. At the core of this approach is\nthe flux summation theorem. This theorem implies that there is an invariant\nrelationship between the control coefficients of enzymes in a pathway. One of\nthe main conclusions that has been derived from the summation theorem is that\nphenotypic robustness to mutation (e.g. dominance) is an inherent property of\nmetabolic systems and hence does not require an evolutionary explanation\n(Kacser \u0026 Burns (1981). Genetics. 97, 639-666; Porteous (1996). J. theor. Biol.\n182, 223-232). Here we show that for mutations involving discrete changes (of\nany magnitude) in enzyme concentration the flux summation theorem does not\nhold. The scenarios we examine are two-enzyme pathways with a diffusion\nbarrier, two enzyme pathways that allow for enzyme saturation and two enzyme\npathways that have both saturable enzymes and a diffusion barrier. Our results\nare extendable to sequential pathways with any number of enzymes. The fact that\nthe flux summation theorem cannot hold in sequential pathways casts serious\ndoubts on the claim that robustness with respect to mutations is an inherent\nproperty of metabolic systems.",
"arxiv_id": "physics/0202026",
"authors": [
"Homayoun Bagheri-Chaichian",
"Joachim Hermisson",
"Juozas R. Vaisnys",
"Gunter P. Wagner"
],
"categories": [
"physics.bio-ph",
"physics.chem-ph",
"q-bio"
],
"title": "The control of phenotype: connecting enzyme variation to physiology",
"url": "https://arxiv.org/abs/physics/0202026"
},
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