Mechanistic basis for nonlinear kinetics of aldehyde reduction catalyzed by aldose reductase

Biochemistry ◽  
1990 ◽  
Vol 29 (42) ◽  
pp. 9947-9955 ◽  
Author(s):  
Charles E. Grimshaw ◽  
M. Shahbaz ◽  
C. G. Putney
Keyword(s):  
Aldose Reductase ◽  
Nonlinear Kinetics ◽  
Mechanistic Basis ◽  
Kinetics Of ◽  
Aldehyde Reduction

scholarly journals Abrogation of prenucleation, transient oligomerization of the Huntingtin exon 1 protein by human profilin I

2020 ◽  
Vol 117 (11) ◽  
pp. 5844-5852 ◽  
Author(s):  
Alberto Ceccon ◽  
Vitali Tugarinov ◽  
Rodolfo Ghirlando ◽  
G. Marius Clore
Keyword(s):  
Single Molecule ◽  
Chemical Exchange ◽  
Coiled Coil ◽  
Relaxation Dispersion ◽  
Line Broadening ◽  
Exon 1 ◽  
Nmr Techniques ◽  
Mechanistic Basis ◽  
Kinetics Of ◽  
Micromolar Range

Human profilin I reduces aggregation and concomitant toxicity of the polyglutamine-containing N-terminal region of the huntingtin protein encoded by exon 1 (httex1) and responsible for Huntington’s disease. Here, we investigate the interaction of profilin with httex1using NMR techniques designed to quantitatively analyze the kinetics and equilibria of chemical exchange at atomic resolution, including relaxation dispersion, exchange-induced shifts, and lifetime line broadening. We first show that the presence of two polyproline tracts in httex1, absent from a shorter huntingtin variant studied previously, modulates the kinetics of the transient branched oligomerization pathway that precedes nucleation, resulting in an increase in the populations of the on-pathway helical coiled-coil dimeric and tetrameric species (τex≤ 50 to 70 μs), while leaving the population of the off-pathway (nonproductive) dimeric species largely unaffected (τex∼750 μs). Next, we show that the affinity of a single molecule of profilin to the polyproline tracts is in the micromolar range (Kdiss∼ 17 and ∼ 31 μM), but binding of a second molecule of profilin is negatively cooperative, with the affinity reduced ∼11-fold. The lifetime of a 1:1 complex of httex1with profilin, determined using a shorter huntingtin variant containing only a single polyproline tract, is shown to be on the submillisecond timescale (τex∼ 600 μs andKdiss∼ 50 μM). Finally, we demonstrate that, in stable profilin–httex1complexes, the productive oligomerization pathway, leading to the formation of helical coiled-coil httex1tetramers, is completely abolished, and only the pathway resulting in “nonproductive” dimers remains active, thereby providing a mechanistic basis for how profilin reduces aggregation and toxicity of httex1.

Thermodynamic Structure of Nonlinear Macrokinetics in Reaction-Diffusion Systems

2004 ◽  
Vol 11 (02) ◽  
pp. 185-202 ◽  
Author(s):  
Stanisław Sieniutycz
Keyword(s):  
Chemical Reactions ◽  
Reaction Diffusion ◽  
Transport Processes ◽  
Mass Action ◽  
Nonlinear Kinetics ◽  
Reaction Diffusion Systems ◽  
Thermodynamic Structure ◽  
Far From Equilibrium ◽  
Physical Consequences ◽  
Kinetics Of

Affinity picture — new for transport phenomena — and the traditional Onsagerian picture are shown to constitute two equivalent representations for kinetics of chemical reactions and transfer processes. Two competing directions in elementary chemical or transport steps are analyzed. Nonequilibrium systems are described by equations of nonlinear kinetics of Marcelin-Kohnstamm-de Donder type that contain terms exponential with respect to the Planck potentials and temperature reciprocal. Simultaneously these equations are analytical expressions characterizing the transport of the substance or energy through the energy barrier. We regard kinetics of this sort as potential representations of a generalized law of mass action that includes the effect of transfer phenomena and external fields. We also consider physical consequences of these kinetics closely and far from equilibrium, and show how diverse processes can be described. In these developments we point out the significance of nonlinear symmetries and generalized affinity. Correspondence with the Onsager's theory is shown in the vicinity of thermodynamic equilibrium. Yet, the theory shows that far from equilibrium the rates of transport processes and chemical reactions cannot be determined uniquely in terms of their affinities because these rates depend on all state coordinates of the system.

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