scholarly journals Quantitative analysis of metabolic regulation. A graph-theoretic approach using spanning trees

1991 ◽  
Vol 275 (1) ◽  
pp. 253-258 ◽  
Author(s):  
A K Sen

A graph-theoretic technique using spanning trees is described for the evaluation of Flux Control Coefficients of metabolic pathways. The technique is illustrated by investigating a linear pathway (a) in the absence of feedback and feedforward regulation. (b) with its first enzyme inhibited by the end product and (c) with multiple feedback loops. It is shown that the Flux Control Coefficients of a linear pathway with one or more feedback loops can be derived in a systematic manner by superimposing the effect of the feedback loop(s) on the expressions pertaining to the Flux Control Coefficients of the unregulated pathway.

1991 ◽  
Vol 279 (1) ◽  
pp. 55-65 ◽  
Author(s):  
A K Sen

Within the premises of the flux-oriented theory of Crabtree & Newsholme [(1987) Biochem. J. 247, 113-120], I have used a graph-theoretic approach for calculating the Control Coefficients of metabolic pathways. It is shown that a directed graph representing the control structure of a metabolic pathway can be constructed in a heuristic manner directly from the reaction diagram of the pathway, without the necessity of writing down the governing equations for the Control Coefficients. The Control Coefficients are derived from an analysis of the topology of the directed graph. The graph-theoretic approach also provides a visual framework for analysing the functional relationships of the individual enzymes. The control structures of the following pathways are examined here: (a) a simple unbranched pathway with four enzymes, (b) a simple branched pathway with three enzymes, and (c) a branched pathway with both carbon and energy (ATP) fluxes.


1992 ◽  
Vol 282 (3) ◽  
pp. 919-927 ◽  
Author(s):  
J Delgado ◽  
J C Liao

Flux Control Coefficients have been used in the analysis of metabolic regulation for quantifying the effect of an enzyme on the overall steady-state flux. However, the experimental determination of these coefficients is very time-consuming, involving either determining the individual enzyme kinetics or perturbing the enzyme activity by genetic or other means. We developed a methodology that enables the determination of the Flux Control Coefficients from transient metabolite concentrations without knowing kinetic parameters. The transient states can be generated by changing the incubation conditions or adding the initial substrate. This approach is suitable for investigating metabolic regulation in vivo or multiple enzyme systems in vitro. It is particularly helpful if used in conjunction with n.m.r. measurements. The approach is based on a relationship between transient metabolite concentrations and the Flux Control Coefficients. The methodology has been improved from our previous results, and it is illustrated by three examples with simple pathway topologies.


Genetics ◽  
2003 ◽  
Vol 165 (4) ◽  
pp. 2235-2247
Author(s):  
Immanuel V Yap ◽  
David Schneider ◽  
Jon Kleinberg ◽  
David Matthews ◽  
Samuel Cartinhour ◽  
...  

AbstractFor many species, multiple maps are available, often constructed independently by different research groups using different sets of markers and different source material. Integration of these maps provides a higher density of markers and greater genome coverage than is possible using a single study. In this article, we describe a novel approach to comparing and integrating maps by using abstract graphs. A map is modeled as a directed graph in which nodes represent mapped markers and edges define the order of adjacent markers. Independently constructed graphs representing corresponding maps from different studies are merged on the basis of their common loci. Absence of a path between two nodes indicates that their order is undetermined. A cycle indicates inconsistency among the mapping studies with regard to the order of the loci involved. The integrated graph thus produced represents a complete picture of all of the mapping studies that comprise it, including all of the ambiguities and inconsistencies among them. The objective of this representation is to guide additional research aimed at interpreting these ambiguities and inconsistencies in locus order rather than presenting a “consensus order” that ignores these problems.


2020 ◽  
Vol 1706 ◽  
pp. 012115
Author(s):  
P Sangeetha ◽  
M Shanmugapriya ◽  
R Sundareswaran ◽  
K Sowmya ◽  
S Srinidhi

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