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Enzyme design for the steady-state of metabolism

University of British Columbia

The steady-state of metabolism has been investigated. The equilibrium thermodynamic properties of metabolic enzymes have been related to their role in the steady-state of metabolism. Simplified free energy profiles that include the reverse reaction have been constructed for the enzyme fumarase under a variety of conditions using the thermodynamic interpretation of the Haldane relationship. The difference in the Gibbs free energy change of activation forward compared to that of the reverse direction (ΔG[sub R]) has been found not to equal the Gibbs free energy change reactants to products. The binding of substrate may be perturbed independently of the catalytic event. It is suggested that this is important in the determination of ΔG[sub R]. ΔG[sub R] may be perturbed to a considerable extent in fumarase. The importance of ΔG[sub R] is suggested to lie in the steady-state of metabolism. Many steady-states, giving different affinities are theoretically possible. Biological systems have selected a continuous steady-state where ΔG[sub R] is numerically equal to affinity over a range of velocities. In order to achieve this steady-state two important conditions must be imposed on the design of the two enzymes sharing a given substrate. The first is that the Km for the shared substrate must be the same in both enzymes. The second is that enzyme concentration must be adjusted. When these two constraints are imposed on the design of the enzymes the magnitude of the steady-state affinity equals the size of ΔG[sub R].

Text

2010-03-26

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http://hdl.handle.net/2429/22655

Zoology

University of British Columbia

Graduate