High resolution metabolic flux determination using stable isotopes and mass spectrometry

Cellular physiology is a combination of many different functions that have to be accurately probed individually and then precisely correlated to each other, in order to reveal the language used by the cell to communicate changes from the environment to gene expression and vice versa. Genes are transcribed to proteins, which catalyze metabolic pathways, whose activity may in return affect gene expression. DNA microarrays allowed the measurement of the full gene expression profile under a particular set of environmental conditions and genetic backgrounds. To understand, however, the correlation between gene expression and the actual metabolic state of the cell, the latter needs to be also determined with high accuracy. This requires that a comprehensive set of variables is defined to describe metabolic activity and reliable methodologies are developed for the accurate determination of such variables. Defining flux as the rate at which material is processed through a metabolic pathway, the fluxes of a metabolic bioreaction network can be employed to provide an overall measure of metabolic activity. A complete and accurate flux map is the phenotypic equivalent of the gene expression profile. In addition, metabolic fluxes, and especially their changes in response to genetic or environmental perturbations, provide insightful information about the distribution of kinetic and regulatory controls in metabolism.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemical Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2001

Author dc:creator

• Klapa, Maria I

Advisor dc:contributor.advisor

• Gregory Stephanopoulos.

• Chemical Engineering.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/8203

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/8203