The Role of Theory in Advancing 21st-Century Biology Catalyzing Transformative Research (2008) / Chapter Skim
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5 How Do Cells Really Work?
5 How Do Cells Really Work?
Pages 81-89
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From page 81... ...
Understanding how this complex milieu developed and varies across different life forms will serve as another profound illustration of the ways that evolution has maintained certain common ancestral features throughout life's history. The theoretical frameworks provided by thermodynamics and the laws of chemical equilibrium have been used productively to study the chemical reactions of life.
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From page 82... ...
Under any given set of conditions, a chemical system will tend to change its properties, including temperature, pressure, and concentration of reactive chemical species, toward a particular stable state called "equilibrium." If the system is perturbed slightly away from its equilibrium state, it will robustly return to equilibrium. If the system is left alone, it will remain at equilibrium indefinitely.
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From page 83... ...
A cell or organism at equilibrium would be dead. Additional assumptions that are appropriate for reactions in dilute aqueous solutions but not in cells and tissues are: • that reaction volumes are infinite; • that the solutions in which reactions occur are dilute, well defined, and homogenous; • that molecules collide due to diffusional motion; and • that concentrations of substrates are higher than concentrations of enzymes.
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From page 84... ...
"Nonspecific" interactions between proteins -- such as those interactions that do not normally occur in aqueous solutions -- are enhanced, and "specific" interactions occur more readily. For example, since chemical equilibrium theory is based on activities, not concentrations, the equilibrium constant for dimerization of a 40,000-kilodalton molecular weight protein is 10 to 40 times greater in a cell than in dilute solution, and its tetramerization is 1,000- to 100,000-fold greater.
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From page 85... ...
However, purified SNARE proteins mediate fusion reactions relatively promiscuously, showing affinities for each other that do not correlate with their known partnerships within the cell. A conceptual framework based on results in aqueous solution would lead to a search for additional specificity "factors"; in this case, however, it appears that the specificity most likely resides in the intricate mechanisms of the localization and orientation of these disparate SNARE proteins within the cell.
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From page 86... ...
Lower image: Structure of the tryptophan synthase complex, which the substrate tunnel highlighted. SOURCE: The Molecular Basis of Substrate Channeling in Journal of Biological Chemistry, Vol.
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From page 87... ...
Conceptually, these turns could be easily removed, especially in a linear DNA template, by diffusional forces that allowed the DNA to spin on its long axis, much as one can unwind an overtwisted telephone cord by allowing the handset to dangle. Nevertheless, within cells, even for linear DNA molecules such as the 40,000 base pair T7 DNA phage genome, transient positive and negative supercoiling occur concomitantly with transcription.
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From page 88... ...
Deep-etch platinum shadowed electron microscopic images are shown.
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From page 89... ...
Are the assemblages found within cells merely storage forms of the enzymes of interest, as is often speculated? Or is it possible that ordered arrays of reagents, in the nuclear matrix, on the surface of membranous vesicles or on the exposed surfaces of proteinaceous arrays provide the advantages of surface catalysis to biological systems?
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