Stavrum2013 - Tryptophan Metabolism in Liver

Stavrum2013 - Tryptophan Metabolism in
Liver

This model is described in the article:

Model of tryptophan
metabolism, readily scalable using tissue-specific gene
expression data.

Stavrum AK, Heiland I, Schuster S,
Puntervoll P, Ziegler M.
J. Biol. Chem. 2013 Nov; 288(48):
34555-34566
Abstract:

Tryptophan is utilized in various metabolic routes including
protein synthesis, serotonin, and melatonin synthesis and the
kynurenine pathway. Perturbations in these pathways have been
associated with neurodegenerative diseases and cancer. Here we
present a comprehensive kinetic model of the complex network of
human tryptophan metabolism based upon existing kinetic data
for all enzymatic conversions and transporters. By integrating
tissue-specific expression data, modeling tryptophan metabolism
in liver and brain returned intermediate metabolite
concentrations in the physiological range. Sensitivity and
metabolic control analyses identified expected key enzymes to
govern fluxes in the branches of the network. Combining
tissue-specific models revealed a considerable impact of the
kynurenine pathway in liver on the concentrations of
neuroactive derivatives in the brain. Moreover, using
expression data from a cancer study predicted metabolite
changes that resembled the experimental observations. We
conclude that the combination of the kinetic model with
expression data represents a powerful diagnostic tool to
predict alterations in tryptophan metabolism. The model is
readily scalable to include more tissues, thereby enabling
assessment of organismal tryptophan metabolism in health and
disease.

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