Kinetic partitioning

From the description of the kinetic partitioning mechanism (KPM) given above it follows that generically the time dependence of the fraction of molecules that have not folded at time t, is given by... 

It is now well understood that fibril formation requires conformational changes, but the assembly steps may differ from one system to another (Kelly, 1998). For example, aggregation into well-ordered structures occurs in multiple steps during the formation of /Mactoglobulin fibrils. First, there is a fast and reversible step followed by an irreversible step involving the formation of nonreversible /1-sheet structures (Arnaudov et al., 2003). Interestingly, the reversible step, which corresponds to a lag in fibril formation, varies from one system to another and most likely depends on the specific kinetic partitioning between the misfolded intermediate and the native state (Dobson, 1999 Jaenicke, 1995 Uversky, 2003). 

At steady-state, solid and liquid far from the interface tend to have the same concentration. Kinetic partitioning therefore brings solid-liquid partition coefficients close to unity and decreases chemical fractionation. The concentration profile in the liquid at distance x from the interface also reads... 

Johnson and Fierke Hammes have presented detailed accounts of how rapid reaction techniques allow one to analyze enzymic catalysis in terms of pre-steady-state events, single-turnover kinetics, substrate channeling, internal equilibria, and kinetic partitioning. See Chemical Kinetics Stopped-Flow Techniques... 

Donlin, M. J., Patel, S. S., and Johnson, K. A. (1991). Kinetic partitioning between the exonuclease and polymerase sites in DNA error correction. Biochemistry 30, 538-546. 

According to this pathway, the rate of disappearance of ES and the rates of formation of EP and of EQ are each governed by a rate equal to the sum = ki + k-i. The kinetic partitioning between EP and EQ will only be re-... 

The kinetic partitioning of enzyme intermediates is an important principle, and the rules governing kinetic partitioning are quite simple. The fractional yield of a given reaction is given simply as the rate of the desired reaction divided by the sum of the rates of all reactions involving the intermediate. For example, consider the forked reaction pathway in Scheme XXI. 

According to this mechanism, the fractional yield of the intermediate to form P is given by the ratio 2/( 2 + -1 + 3)- The importance of kinetic partitioning will be illustrated by two examples. 

For a sequential bisubstrate enzyme, the rate of dissociation of the hrst substrate can be estimated by substrate trapping methods. The rationale for this experimental approach is shown in Scheme XXII. The enzyme is first preincubated with radiolabeled substrate A and is then mixed with an excess of unlabeled substrate A and substrate B to initiate the reaction. The recovery of radio-labeled product is a function of the kinetic partitioning of the enzyme-bound substrate between dissociation to yield free S and forward reaction with substrate B to yield product P. 

Fig. 13. DNA polymerase kinetic partitioning. The pathway shows the potential reactions during DNA replication polymerization (tpoi), dissociation of the E-DNA complex (kotr). pyrophosphoro-lysis (kpp), and exonuclease digestion of the 3 -terminal base (k xo)- Reproduced with permission from (/7).

Chiti F, Taddei N, Baroni F, Capanni C, Stefani M, Ramponi G et al (2002) Kinetic partitioning of protein folding and aggregation. Nat Struct Biol 9(2) 137-143... 

Frank BL, Worth Jr L, Christner DF, et al. Isotope effects on the sequence-specific cleavage of DNA by neocaranostatin kinetic partitioning between 4 - and 5 -hydrogen abstraction at nniqne thymidine sites.Chem Soc. 1991 113 2271—2275. Stubbe J, KozarichJW. Mechanisms of bleomycin-induced DNA degradation. Chem Rev. 1987 87 1107-1136. 

The same sense of elimination to form the more stable alkene (the Saytzeff-type product) can also be observed in cyclic systems. For example, as shown in Scheme 7.30, the unstable tertiary iodide 1,2-dimethyliodocyclohexane undergoes elimination to a mixture of three alkenes, viz. 1,2-dimethylcyclohexene, 23-dimethylcyclohexene, and 2-methyl-l-methylenecyclohexane, the ratio of which (6631 3) clearly represents some kinetic partitioning between tetrasubstituted ... 

B. Moderate Folders, Topological Frustration, and Kinetic Partitioning Mechanism VI. Disulfide Bonds in Folding... 

Sinclair, J.F., Ziegler, M.M., and Baldwin, TO., Kinetic partitioning during protein folding yields multiple native states. Nature Struct. Biol, 1, 320,1994. 

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