Unformatted text preview: s out to quantify the distribution of control within a pathway.
The degree of control by an enzyme (or group of enzymes) is described
quantitatively in the form of flux control coefficients (see next slide).
1 It also can be used to assess the control over the concentrations of the
metabolites in a pathway. The distribution of control over metabolite
concentrations is described quantitatively in the form of concentration
2 What is a flux control coefficient?
A flux control coefficient describes quantitatively how much control a
step (or block of steps) has over the flux through a pathway.
Flux control coefficients range from -1 to +1
If some perturbation of an enzyme increases its rate by 5%, and the
whole pathway by 2%, the enzyme is said to have a flux control
coefficient of 2/5, or 0.4.
If another perturbation of another enzyme causes its rate to increase by
5%, but the activity of the whole pathway decreases by 2%, the enzyme
is said to have a flux control coefficient of -2/5 = -0.4.
The sum of all coefficients for a pathway equals 1
(This is called the summation theorem) 0.40
D E Flux Control Coefficients in a
Branched Metabolic Pathway
For flux A to D
For Note that the Summation Theorem holds for branched pathways too
Note Applications of Metabolic
Control Medical research
What enzymes in a given pathway become disordered
in a given disease? • E.g., Altered activity of glycolytic enzymes – implications for
pathologies associated with diabetes (retinopathy, neuropathy)
• E.g., hyperthyroidism and impaired oxidative phosphorylation Can
Can pharmaceuticals be better designed to normalize
metabolic fluxes in disease?
Metabolomics Number of publications per year The field of metabolomics is growing ! Metabolomics: The comprehensive and quantitative analysis of
all metabolites in a biological system Avoids exclusion of any metabolites
Allows high sample throughput capabilities
Attempts to incorporate findings into a broader picture, to improve
the understanding of biochemical networks
It is a systems biology approach Metabolite: Any organic molecule with a MW < 1000 Da Includes peptides, oligonucleotides, sugars, nucelosides,
organic acids, ketones, aldehydes, amines, amino acids,
lipids, steroids, and drugs (xenobiotics)
Metabolome: a comprehensive term used to describe all the
possible metabolites for a biological system (just as genome and
proteome refer to all possible genes and proteins) ‘omics’ Genomics 30,000
+++ Metabolites Proteomics Metabolomics Sample Metabolite List
Sample (+)-(-)-Methylsuccinic Acid
DL-B-Aminoisobutyric Acid DL-Carnitine
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- Winter '11
- Enzyme, Carboxylic acid, free energy change, Metabolomics